{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:26:44Z","timestamp":1790519204406,"version":"4.1.0"},"reference-count":205,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Breast Cancer Foundation"},{"name":"Women and Children\u2019s Health Institute of the University of Alberta (WCHRI)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance. In this review, we will summarize recent advances made in understanding LPA signaling with respect to chronic inflammation and cancer. We will also provide perspectives on the applications of inhibitors of LPA signaling in preventing cancer initiation, as adjuncts extending the efficacy of current cancer treatments by blocking inflammation caused by either the cancer or the cancer therapy itself, and by disruption of the tumor microenvironment. Overall, LPA, a simple molecule that mediates a plethora of biological effects, can be targeted at its levels of production by autotaxin, LPA receptors or through LPA degradation by lipid phosphate phosphatases. Drugs for these applications will soon be entering clinical practice.<\/jats:p>","DOI":"10.3390\/cancers10030073","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T05:11:28Z","timestamp":1521090688000},"page":"73","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-684X","authenticated-orcid":false,"given":"Matthew","family":"Benesch","sequence":"first","affiliation":[{"name":"Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John\u2019s, NL AlB 3V6, Canada"},{"name":"Signal Transduction Research Group, Cancer Research Institute of Northern Alberta, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"MacIntyre","sequence":"additional","affiliation":[{"name":"Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John\u2019s, NL AlB 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"McMullen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brindley","sequence":"additional","affiliation":[{"name":"Signal Transduction Research Group, Cancer Research Institute of Northern Alberta, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1056\/NEJM198612253152606","article-title":"Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing","volume":"315","author":"Dvorak","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.coi.2010.01.009","article-title":"Macrophages, innate immunity and cancer: Balance, tolerance, and diversity","volume":"22","author":"Mantovani","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/carcin\/bgp127","article-title":"Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability","volume":"30","author":"Colotta","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1158\/1078-0432.CCR-15-1374","article-title":"Molecular pathways: The balance between cancer and the immune system challenges the therapeutic specificity of targeting nuclear factor-\u03bab signaling for cancer treatment","volume":"22","author":"Zeligs","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: Functions of cells recruited to the tumor microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.trecan.2017.07.006","article-title":"Targeting inflammation to improve tumor drug delivery","volume":"3","author":"Gkretsi","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1126\/science.337.6092.282","article-title":"Profile: Bert vogelstein. Cancer genetics with an edge","volume":"337","author":"Kaiser","year":"2012","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/bjc.2014.90","article-title":"Cancer and systemic inflammation: Treat the tumour and treat the host","volume":"110","author":"Roxburgh","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Brindley, D.N., Benesch, M.G.K., and Murph, M.M. (2015). Autotaxin\u2014An enzymatic augmenter of malignant progression linked to inflammation. Melanoma\u2014Current Clinical Management and Future Therapeutics, InTech Open.","DOI":"10.5772\/59013"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"272","DOI":"10.7555\/JBR.30.20150058","article-title":"Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo","volume":"30","author":"Benesch","year":"2016","journal-title":"J. Biomed. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.trecan.2017.09.004","article-title":"Lysophosphatidate signaling: The tumor microenvironment\u2019s new nemesis","volume":"3","author":"Benesch","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1016\/j.febslet.2014.02.009","article-title":"Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions","volume":"588","author":"Benesch","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1128\/MCB.02419-05","article-title":"Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development","volume":"26","author":"Ruurs","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25822","DOI":"10.1074\/jbc.M605142200","article-title":"Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid","volume":"281","author":"Tanaka","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1124\/jpet.110.165845","article-title":"A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation","volume":"334","author":"Gierse","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1194\/jlr.M014985","article-title":"Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid","volume":"52","author":"Dusaulcy","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Quan, M., Cui, J.J., Feng, X., and Huang, Q. (2017). The critical role and potential target of the autotaxin\/lysophosphatidate axis in pancreatic cancer. Tumour Biol., 39.","DOI":"10.1177\/1010428317694544"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbrc.2010.03.169","article-title":"GPR35 is a novel lysophosphatidic acid receptor","volume":"395","author":"Oka","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.bbrc.2007.09.063","article-title":"The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor","volume":"363","author":"Tabata","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejphar.2013.06.029","article-title":"GPR87 mediates lysophosphatidic acid-induced colony dispersal in A431 cells","volume":"715","author":"Ochiai","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.bbrc.2008.04.145","article-title":"Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor","volume":"371","author":"Murakami","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1084\/jem.20120873","article-title":"Lysophosphatidic acid targets vascular and oncogenic pathways via rage signaling","volume":"209","author":"Rai","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1194\/jlr.M065086","article-title":"Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate","volume":"57","author":"Tang","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1194\/jlr.R058362","article-title":"Lipid phosphate phosphatases and their roles in mammalian physiology and pathology","volume":"56","author":"Tang","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/jb\/mvu077","article-title":"Lysophosphatidic acid as a lipid mediator with multiple biological actions","volume":"157","author":"Aikawa","year":"2015","journal-title":"J. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1194\/jlr.R046458","article-title":"LPA receptor signaling: Pharmacology, physiology, and pathophysiology","volume":"55","author":"Yung","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Riaz, A., Huang, Y., and Johansson, S. (2016). G-protein-coupled lysophosphatidic acid receptors and their regulation of AKT signaling. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020215"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.yexcr.2015.03.016","article-title":"Lysophospholipid mediators in the vasculature","volume":"333","author":"Mueller","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1387\/ijdb.092879km","article-title":"Ectophosphodiesterase\/nucleotide phosphohydrolase (Enpp) nucleotidases: Cloning, conservation and developmental restriction","volume":"54","author":"Masse","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1194\/jlr.R060020","article-title":"Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression","volume":"57","author":"Federico","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nsmb.1998","article-title":"Crystal structure of autotaxin and insight into GPCR activation by lipid mediators","volume":"18","author":"Nishimasu","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1074\/jbc.M116.774356","article-title":"Selective export of autotaxin from the endoplasmic reticulum","volume":"292","author":"Lyu","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1242\/jcs.02438","article-title":"Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D","volume":"118","author":"Jansen","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39436","DOI":"10.1074\/jbc.M205623200","article-title":"Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase","volume":"277","author":"Tokumura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1083\/jcb.200204026","article-title":"Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production","volume":"158","author":"Kishi","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1016\/S0021-9258(18)45911-X","article-title":"Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein","volume":"267","author":"Stracke","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1194\/jlr.R046391","article-title":"Autotaxin: Structure-function and signaling","volume":"55","author":"Perrakis","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nsmb0211-117","article-title":"Location, location, location: A crystal-clear view of autotaxin saturating LPA receptors","volume":"18","author":"Tabchy","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.bbrc.2016.12.154","article-title":"Proliferation of mouse endometrial stromal cells in culture is highly sensitive to lysophosphatidic acid signaling","volume":"484","author":"Aikawa","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.theriogenology.2017.09.027","article-title":"Bovine ovarian follicular growth and development correlate with lysophosphatidic acid expression","volume":"106","author":"Sinderewicz","year":"2017","journal-title":"Theriogenology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12958-017-0287-9","article-title":"Expression of factors involved in apoptosis and cell survival is correlated with enzymes synthesizing lysophosphatidic acid and its receptors in granulosa cells originating from different types of bovine ovarian follicles","volume":"15","author":"Sinderewicz","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6600","DOI":"10.1111\/febs.12565","article-title":"Autotaxin as a novel, tissue-remodeling-related factor in regressing corpora lutea of cycling rats","volume":"280","author":"Masuda","year":"2013","journal-title":"FEBS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/jog.12742","article-title":"Placental autotaxin expression is diminished in women with pre-eclampsia","volume":"41","author":"Ichikawa","year":"2015","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/10641955.2017.1388389","article-title":"Maternal serum autotaxin levels in early- and late-onset preeclampsia","volume":"36","author":"Erenel","year":"2017","journal-title":"Hypertens. Pregnancy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3572","DOI":"10.1016\/j.febslet.2007.06.064","article-title":"Functional invalidation of the autotaxin gene by a single amino acid mutation in mouse is lethal","volume":"581","author":"Ferry","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ydbio.2010.01.007","article-title":"ATX expression and LPA signalling are vital for the development of the nervous system","volume":"339","author":"Fotopoulou","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/glia.22381","article-title":"Autotaxin\/ENPP2 regulates oligodendrocyte differentiation in vivo in the developing zebrafish hindbrain","volume":"60","author":"Yuelling","year":"2012","journal-title":"Glia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11399","DOI":"10.1523\/JNEUROSCI.0345-15.2015","article-title":"The autotaxin-lysophosphatidic acid axis modulates histone acetylation and gene expression during oligodendrocyte differentiation","volume":"35","author":"Wheeler","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.1242\/dev.081745","article-title":"Autotaxin\/Lpar3 signaling regulates Kupffer\u2019s vesicle formation and left-right asymmetry in zebrafish","volume":"139","author":"Lai","year":"2012","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yukiura, H., Kano, K., Kise, R., Inoue, A., and Aoki, J. (2015). Autotaxin overexpression causes embryonic lethality and vascular defects. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126734"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1242\/dev.00635","article-title":"The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning","volume":"130","author":"Hernandez","year":"2003","journal-title":"Development"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/cvr\/cvw090","article-title":"Endothelial lipid phosphate phosphatase-3 deficiency that disrupts the endothelial barrier function is a modifier of cardiovascular development","volume":"111","author":"Chatterjee","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37678","DOI":"10.1038\/srep37678","article-title":"Role of ectonucleotide pyrophosphatase\/phosphodiesterase 2 in the midline axis formation of zebrafish","volume":"6","author":"Frisca","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/jb\/mvt114","article-title":"Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo","volume":"155","author":"Nakanaga","year":"2014","journal-title":"J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jb\/mvq052","article-title":"Autotaxin\u2014An LPA producing enzyme with diverse functions","volume":"148","author":"Nakanaga","year":"2010","journal-title":"J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"851","DOI":"10.4049\/jimmunol.1302831","article-title":"The autotaxin-LPA axis emerges as a novel regulator of lymphocyte homing and inflammation","volume":"192","author":"Knowlden","year":"2014","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1182\/blood-2016-10-743757","article-title":"Lysophosphatidic acid converts monocytes into macrophages in both mice and humans","volume":"129","author":"Ray","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"34654","DOI":"10.1074\/jbc.M111.276725","article-title":"Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells","volume":"286","author":"Fulkerson","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Song, J., Guan, M., Zhao, Z., and Zhang, J. (2015). Type I interferons function as autocrine and paracrine factors to induce autotaxin in response to TLR activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136629"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"617","DOI":"10.4049\/jimmunol.1400565","article-title":"Autotaxin produced by stromal cells promotes LFA-1-independent and Rho-dependent interstitial T cell motility in the lymph node paracortex","volume":"193","author":"Katakai","year":"2014","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Knowlden, S.A., Capece, T., Popovic, M., Chapman, T.J., Rezaee, F., Kim, M., and Georas, S.N. (2014). Regulation of T cell motility in vitro and in vivo by LPA and LPA2. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101655"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e10561","DOI":"10.7554\/eLife.10561","article-title":"Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility","volume":"5","author":"Takeda","year":"2016","journal-title":"eLife"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12478","DOI":"10.1073\/pnas.1608564113","article-title":"Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program","volume":"113","author":"Kime","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40478-017-0446-4","article-title":"Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis","volume":"5","author":"Schmitz","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Raddatz, B.B., Hansmann, F., Spitzbarth, I., Kalkuhl, A., Deschl, U., Baumgartner, W., and Ulrich, R. (2014). Transcriptomic meta-analysis of multiple sclerosis and its experimental models. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086643"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s11064-008-9772-z","article-title":"Lysophosphatidic acid can support the formation of membranous structures and an increase in MBP mRNA levels in differentiating oligodendrocytes","volume":"34","author":"Nogaroli","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1124\/jpet.116.234013","article-title":"Pharmacological characterization of a potent inhibitor of autotaxin in animal models of inflammatory bowel disease and multiple sclerosis","volume":"359","author":"Thirunavukkarasu","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"23433","DOI":"10.1038\/srep23433","article-title":"ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation","volume":"6","author":"Nishioka","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1902\/jop.2009.080624","article-title":"Lysophosphatidic acid signals through specific lysophosphatidic acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts","volume":"80","author":"George","year":"2009","journal-title":"J. Periodontol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.gdata.2014.10.014","article-title":"Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts","volume":"2","author":"Cerutis","year":"2014","journal-title":"Genom. Data"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1902\/jop.2015.140592","article-title":"A major human oral lysophosphatidic acid species, LPA 18:1, regulates novel genes in human gingival fibroblasts","volume":"86","author":"Cerutis","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1194\/jlr.M057661","article-title":"Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate","volume":"56","author":"Benesch","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.canlet.2009.04.029","article-title":"Rapid clearance of the circulating metastatic factor autotaxin by the scavenger receptors of liver sinusoidal endothelial cells","volume":"284","author":"Jansen","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1084\/jem.20112012","article-title":"Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis","volume":"209","author":"Nikitopoulou","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1165\/rcmb.2012-0004OC","article-title":"Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis","volume":"47","author":"Oikonomou","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1002\/hep.28973","article-title":"Hepatocyte autotaxin expression promotes liver fibrosis and cancer","volume":"65","author":"Kaffe","year":"2017","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.plipres.2017.11.002","article-title":"Adipocyte biology in breast cancer: From silent bystander to active facilitator","volume":"69","author":"Choi","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s13105-012-0181-z","article-title":"Depot-specific regulation of autotaxin with obesity in human adipose tissue","volume":"68","author":"Rancoule","year":"2012","journal-title":"J. Physiol. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Nakamura, R., Okura, T., Fujioka, Y., Sumi, K., Matsuzawa, K., Izawa, S., Ueta, E., Kato, M., Taniguchi, S.I., and Yamamoto, K. (2017). Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, a clinical study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179737"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1210\/en.2017-00035","article-title":"Autotaxin is regulated by glucose and insulin in adipocytes","volume":"158","author":"Kane","year":"2017","journal-title":"Endocrinology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1515\/hmbci-2013-0053","article-title":"The role of leptin\/adiponectin ratio in metabolic syndrome and diabetes","volume":"18","year":"2014","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cmet.2016.04.011","article-title":"Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk","volume":"23","author":"Stern","year":"2016","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6619","DOI":"10.1038\/s41598-017-06997-0","article-title":"Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome","volume":"7","author":"Fruhbeck","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1002\/oby.21232","article-title":"Serum Autotaxin\/ENPP2 correlates with insulin resistance in older humans with obesity","volume":"23","author":"Reeves","year":"2015","journal-title":"Obesity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1210\/me.2011-1229","article-title":"Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice","volume":"26","author":"Federico","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1159\/000480470","article-title":"Lysophosphatidic acid inhibits insulin signaling in primary rat hepatocytes via the LPA3 receptor subtype and is increased in obesity","volume":"43","author":"Fayyaz","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1194\/jlr.M075655","article-title":"Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity","volume":"58","author":"Sun","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.2337\/db13-1694","article-title":"ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity","volume":"63","author":"Nishimura","year":"2014","journal-title":"Diabetes"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2169\/internalmedicine.55.5473","article-title":"Serum autotaxin levels are associated with proteinuria and kidney lesions in japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy","volume":"55","author":"Shimizu","year":"2016","journal-title":"Intern. Med."},{"key":"ref_95","first-page":"9173090","article-title":"Autotaxin-lysophosphatidic acid: From inflammation to cancer development","volume":"2017","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3389\/fphys.2017.00266","article-title":"Lysophosphatidic acid is associated with atherosclerotic plaque instability by regulating NF-\u03bab dependent matrix metalloproteinase-9 expression via LPA2 in macrophages","volume":"8","author":"Gu","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/joim.12519","article-title":"Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease","volume":"280","author":"Nsaibia","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1080\/14779072.2017.1367286","article-title":"Pathobiology of Lp(a) in calcific aortic valve disease","volume":"15","author":"Mathieu","year":"2017","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCULATIONAHA.115.016757","article-title":"Autotaxin derived from lipoprotein(a) and valve interstitial cells promotes inflammation and mineralization of the aortic valve","volume":"132","author":"Bouchareb","year":"2015","journal-title":"Circulation"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1161\/ATVBAHA.113.302737","article-title":"Arguing the case for the autotaxin-lysophosphatidic acid-lipid phosphate phosphatase 3-signaling nexus in the development and complications of atherosclerosis","volume":"34","author":"Smyth","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/cvr\/cvw217","article-title":"Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function","volume":"112","author":"Weidmann","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/ATVBAHA.113.302335","article-title":"Mice with targeted inactivation of Ppap2b in endothelial and hematopoietic cells display enhanced vascular inflammation and permeability","volume":"34","author":"Panchatcharam","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12974-016-0530-x","article-title":"Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research","volume":"13","author":"Parimisetty","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3233\/JAD-160891","article-title":"Autotaxin is related to metabolic dysfunction and predicts alzheimer\u2019s disease outcomes","volume":"56","author":"McLimans","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuropharm.2016.04.002","article-title":"Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain","volume":"113","author":"Velasco","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.joca.2016.08.016","article-title":"Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain","volume":"25","author":"McDougall","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Herr, D.R., Ong, J.H., and Ong, W.Y. (2018). Potential therapeutic applications for inhibitors of autotaxin, a bioactive lipid-producing lysophospholipase D, in disorders affecting the nervous system. ACS Chem. Neurosci.","DOI":"10.1021\/acschemneuro.8b00057"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cca.2015.01.032","article-title":"Plasma and synovial fluid autotaxin correlate with severity in knee osteoarthritis","volume":"444","author":"Mabey","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1038\/s41598-017-07963-6","article-title":"High-fat diet-induced acceleration of osteoarthritis is associated with a distinct and sustained plasma metabolite signature","volume":"7","author":"Datta","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejphar.2015.08.028","article-title":"The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid arthritis","volume":"765","author":"Orosa","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_111","first-page":"17117","article-title":"Autotaxin-LPA receptor axis in the pathogenesis of lung diseases","volume":"8","author":"Chu","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nm1685","article-title":"The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak","volume":"14","author":"Tager","year":"2008","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1096\/fj.201500197R","article-title":"Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis","volume":"30","author":"Black","year":"2016","journal-title":"FASEB J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1172\/JCI88896","article-title":"Autocrine lysophosphatidic acid signaling activates \u03b2-catenin and promotes lung allograft fibrosis","volume":"127","author":"Cao","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s11302-015-9463-6","article-title":"Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2\/autotaxin exacerbates hyperoxic lung injury","volume":"11","author":"Lange","year":"2015","journal-title":"Purinergic Signal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2217\/bmm.15.93","article-title":"Polyunsaturated lysophosphatidic acid as a potential asthma biomarker","volume":"10","author":"Ackerman","year":"2016","journal-title":"Biomark. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"27240","DOI":"10.18632\/oncotarget.15916","article-title":"Inhibition of lysophosphatidic acid receptor ameliorates Sjogren\u2019s syndrome in NOD mice","volume":"8","author":"Park","year":"2017","journal-title":"Oncotarget"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1159\/000459706","article-title":"Diabetic macular edema: Emerging strategies and treatment algorithms","volume":"60","author":"Moisseiev","year":"2017","journal-title":"Dev. Ophthalmol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1097\/IAE.0000000000001112","article-title":"Lysophosphatidic acids and autotaxin in retinal vein occlusion","volume":"36","author":"Dacheva","year":"2016","journal-title":"Retina"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/1354750X.2014.994564","article-title":"Serum autotaxin levels correlate with hepatic dysfunction and severity in postoperative biliary atresia","volume":"20","author":"Udomsinprasert","year":"2015","journal-title":"Biomarkers"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Udomsinprasert, W., Kitkumthorn, N., Mutirangura, A., Chongsrisawat, V., Poovorawan, Y., and Honsawek, S. (2017). Association between promoter hypomethylation and overexpression of autotaxin with outcome parameters in biliary atresia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169306"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e1311827","DOI":"10.1080\/23723556.2017.1311827","article-title":"The autotaxin-lysophosphatidic acid pathway emerges as a therapeutic target to prevent liver cancer","volume":"4","author":"Erstad","year":"2017","journal-title":"Mol. Cell. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1158\/0008-5472.CAN-14-1607","article-title":"Lysophosphatidic acid receptor LPAR6 supports the tumorigenicity of hepatocellular carcinoma","volume":"75","author":"Mazzocca","year":"2015","journal-title":"Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/oby.20960","article-title":"Serum autotaxin is independently associated with hepatic steatosis in women with severe obesity","volume":"23","author":"Rachakonda","year":"2015","journal-title":"Obesity"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.autrev.2016.03.019","article-title":"Autotaxin, pruritus and primary biliary cholangitis (PBC)","volume":"15","author":"Sun","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.cca.2012.07.014","article-title":"Autotaxin in liver fibrosis","volume":"413","author":"Ikeda","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"30847","DOI":"10.1038\/srep30847","article-title":"Serum autotaxin is a marker of the severity of liver injury and overall survival in patients with cholestatic liver diseases","volume":"6","author":"Wunsch","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Ringelhan, M., McKeating, J.A., and Protzer, U. (2017). Viral hepatitis and liver cancer. Philos. Trans. R. Soc. Lond. B Biol. Sci., 372.","DOI":"10.1098\/rstb.2016.0274"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Ikeda, H., Kobayashi, M., Kumada, H., Enooku, K., Koike, K., Kurano, M., Sato, M., Nojiri, T., Kobayashi, T., and Ohkawa, R. (2017). Annals express: Performance of autotaxin as a serum marker of liver fibrosis. Ann. Clin. Biochem.","DOI":"10.1177\/0004563217741509"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/hepr.12997","article-title":"Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection","volume":"48","author":"Joshita","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"46705","DOI":"10.1038\/srep46705","article-title":"Association of serum autotaxin levels with liver fibrosis in patients with chronic hepatitis C","volume":"7","author":"Yamazaki","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.jhep.2017.01.009","article-title":"Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication","volume":"66","author":"Farquhar","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/infdis\/jiw372","article-title":"During Hepatitis C Virus (HCV) infection and HCV-HIV coinfection, an elevated plasma level of autotaxin is associated with lysophosphatidic acid and markers of immune activation that normalize during interferon-free HCV therapy","volume":"214","author":"Kostadinova","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jhep.2017.09.016","article-title":"Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine","volume":"68","author":"Fujiwara","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/nsmb.1980","article-title":"Structural basis of substrate discrimination and integrin binding by autotaxin","volume":"18","author":"Hausmann","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.canlet.2016.05.022","article-title":"Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-\u03b2 pathways","volume":"379","author":"Liu","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1096\/fj.15-274480","article-title":"Tumor-induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression","volume":"29","author":"Benesch","year":"2015","journal-title":"FASEB J."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1096\/fj.13-232868","article-title":"Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration","volume":"28","author":"Wu","year":"2014","journal-title":"FASEB J."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.plipres.2015.02.001","article-title":"Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer","volume":"58","author":"Barbayianni","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/carcin\/bgx100","article-title":"ATM-activated autotaxin (ATX) propagates inflammation and DNA damage in lung epithelial cells; a new mode of action for silica-induced DNA damage?","volume":"38","author":"Zheng","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"25823","DOI":"10.1074\/jbc.M116.756908","article-title":"Autotaxin expression is regulated at the post-transcriptional level by the RNA-binding proteins HuR and AUF1","volume":"291","author":"Sun","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1479-828X.2008.00937.x","article-title":"Hur expression in the nucleus correlates with high histological grade and poor disease-free survival in ovarian cancer","volume":"49","author":"Yi","year":"2009","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1007\/s13277-013-0774-3","article-title":"Cytoplasmic HuR expression correlates with P-gp, HER-2 positivity, and poor outcome in breast cancer","volume":"34","author":"Zhu","year":"2013","journal-title":"Tumour Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1530\/ERC-15-0045","article-title":"Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer","volume":"22","author":"Benesch","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"63388","DOI":"10.18632\/oncotarget.11255","article-title":"Identification of tumorigenesis-related mRNAs associated with RNA-binding protein HuR in thyroid cancer cells","volume":"7","author":"Baldan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ccr.2009.03.027","article-title":"Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases","volume":"15","author":"Liu","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1096\/fj.13-248641","article-title":"Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice","volume":"28","author":"Benesch","year":"2014","journal-title":"FASEB J."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1158\/1940-6207.CAPR-15-0107","article-title":"Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation","volume":"9","author":"Volden","year":"2016","journal-title":"Cancer Prev. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/1477-3163.119606","article-title":"Obesity, metabolism and the microenvironment: Links to cancer","volume":"12","author":"Sundaram","year":"2013","journal-title":"J. Carcinog."},{"key":"ref_150","first-page":"291546","article-title":"Obesity as a major risk factor for cancer","volume":"2013","author":"Silvestris","year":"2013","journal-title":"J. Obes."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Memet, I., Tsalkidou, E., Tsaroucha, A.K., Lambropoulou, M., Chatzaki, E., Trypsianis, G., Schizas, D., Pitiakoudis, M., and Simopoulos, C. (2017). Autotaxin expression in hepatocellular carcinoma. J. Investig. Surg., 1\u20137.","DOI":"10.1080\/08941939.2017.1331280"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Enooku, K., Uranbileg, B., Ikeda, H., Kurano, M., Sato, M., Kudo, H., Maki, H., Koike, K., Hasegawa, K., and Kokudo, N. (2016). Higher LPA2 and LPA6 mRNA levels in hepatocellular carcinoma are associated with poorer differentiation, microvascular invasion and earlier recurrence with higher serum autotaxin levels. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161825"},{"key":"ref_153","first-page":"277","article-title":"Implications of the lysophosphatidic acid signaling axis in liver cancer","volume":"1868","author":"Lopane","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.clinbiochem.2011.03.128","article-title":"Specific increase in serum autotaxin activity in patients with pancreatic cancer","volume":"44","author":"Nakai","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Kadekar, S., Silins, I., Korhonen, A., Dreij, K., Al-Anati, L., Hogberg, J., and Stenius, U. (2012). Exocrine pancreatic carcinogenesis and autotaxin expression. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043209"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1194\/jlr.P072090","article-title":"Analysis of glycero-lysophospholipids in gastric cancerous ascites","volume":"58","author":"Emoto","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexcr.2017.10.018","article-title":"Diagnostic and prognostic biomarkers in ovarian cancer and the potential roles of cancer stem cells\u2014An updated review","volume":"362","author":"Muinao","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/stem.2279","article-title":"Autotaxin regulates maintenance of ovarian cancer stem cells through lysophosphatidic acid-mediated autocrine mechanism","volume":"34","author":"Seo","year":"2016","journal-title":"Stem Cells"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.3892\/or.2015.4216","article-title":"The significance of the altered expression of lysophosphatidic acid receptors, autotaxin and phospholipase A2 as the potential biomarkers in type 1 endometrial cancer biology","volume":"34","author":"Wasniewski","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11010-017-2971-7","article-title":"Enhanced cellular functions through induction of LPA2 by cisplatin in fibrosarcoma HT1080 cells","volume":"431","author":"Takahashi","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/stem.2499","article-title":"A lysophosphatidic acid receptors 1 and 3 axis governs cellular senescence of mesenchymal stromal cells and promotes growth and vascularization of multiple myeloma","volume":"35","author":"Kanehira","year":"2017","journal-title":"Stem Cells"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"10656","DOI":"10.1038\/ncomms10656","article-title":"Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer","volume":"7","author":"Hashimoto","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1158\/0008-5472.CAN-12-2424","article-title":"Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and autotaxin","volume":"72","author":"Braeuer","year":"2012","journal-title":"Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1158\/0008-5472.CAN-15-2511","article-title":"NFAT1 directly regulates IL8 and MMP3 to promote melanoma tumor growth and metastasis","volume":"76","author":"Shoshan","year":"2016","journal-title":"Cancer Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/1541-7786.MCR-14-0263","article-title":"Autotaxin and LPA1 and LPA5 receptors exert disparate functions in tumor cells versus the host tissue microenvironment in melanoma invasion and metastasis","volume":"13","author":"Lee","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_166","unstructured":"Lee, S.C., Fujiwara, Y., and Tigyi, G.J. (2015). Uncovering unique roles of LPA receptors in the tumor microenvironment. Recept. Clin. Investig., 2."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1194\/jlr.M053462","article-title":"Lipid phosphate phosphatase-1 expression in cancer cells attenuates tumor growth and metastasis in mice","volume":"55","author":"Tang","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_168","first-page":"1073","article-title":"The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: Validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer","volume":"63","author":"Tanyi","year":"2003","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"14003","DOI":"10.18632\/oncotarget.14776","article-title":"Genome-wide screen identifies a novel prognostic signature for breast cancer survival","volume":"8","author":"Mao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"9297","DOI":"10.1074\/jbc.M511710200","article-title":"Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts","volume":"281","author":"Morris","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1158\/1535-7163.MCT-08-0636","article-title":"Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets","volume":"8","author":"Flanagan","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12943-017-0607-x","article-title":"Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-\u03bab activation","volume":"16","author":"Tang","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1080\/13543776.2017.1323331","article-title":"Autotaxin inhibitors: A patent review (2012\u20132016)","volume":"27","author":"Nikolaou","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.1016\/j.bmcl.2016.10.036","article-title":"Discovery of potent inhibitors of the lysophospholipase autotaxin","volume":"26","author":"Shah","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.plipres.2015.01.004","article-title":"Lysophosphatidic acid receptor (LPAR) modulators: The current pharmacological toolbox","volume":"58","author":"Ghassemian","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Katsifa, A., Kaffe, E., Nikolaidou-Katsaridou, N., Economides, A.N., Newbigging, S., McKerlie, C., and Aidinis, V. (2015). The bulk of autotaxin activity is dispensable for adult mouse life. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143083"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1002\/art.39797","article-title":"An autotaxin\/lysophosphatidic acid\/interleukin-6 amplification loop drives scleroderma fibrosis","volume":"68","author":"Castelino","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/art.30262","article-title":"Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma","volume":"63","author":"Castelino","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.2147\/DDDT.S99696","article-title":"Spotlight on tocilizumab and its potential in the treatment of systemic sclerosis","volume":"10","author":"Sakkas","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.116.237156","article-title":"Selective inhibition of autotaxin is efficacious in mouse models of liver fibrosis","volume":"360","author":"Bain","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.ccell.2016.11.004","article-title":"Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition","volume":"30","author":"Nakagawa","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Mouratis, M.A., Magkrioti, C., Oikonomou, N., Katsifa, A., Prestwich, G.D., Kaffe, E., and Aidinis, V. (2015). Autotaxin and endotoxin-induced acute lung injury. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133619"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.joca.2016.09.006","article-title":"Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain","volume":"25","author":"Thirunavukkarasu","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nsmb.3200","article-title":"Structural basis for specific inhibition of autotaxin by a DNA aptamer","volume":"23","author":"Kato","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"11248","DOI":"10.1038\/ncomms11248","article-title":"Steroid binding to autotaxin links bile salts and lysophosphatidic acid signalling","volume":"7","author":"Keune","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1096\/fj.14-262659","article-title":"Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes involved in drug resistance and oxidative stress responses: Implications for cancer treatment","volume":"29","author":"Venkatraman","year":"2015","journal-title":"FASEB J."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"21164","DOI":"10.1038\/srep21164","article-title":"Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: Implications for tamoxifen therapy and resistance","volume":"6","author":"Bekele","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.cellsig.2015.05.015","article-title":"The autotaxin-LPA2 GPCR axis is modulated by gamma-irradiation and facilitates DNA damage repair","volume":"27","author":"Balogh","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.mrfmmm.2015.06.007","article-title":"Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ros independent manner in cancer cells","volume":"779","author":"Jayakumar","year":"2015","journal-title":"Mutat. Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.freeradbiomed.2015.04.035","article-title":"Nrf2 promotes survival following exposure to ionizing radiation","volume":"88","author":"Sekhar","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.critrevonc.2013.09.001","article-title":"Nrf2 is a potential therapeutic target in radioresistance in human cancer","volume":"88","author":"Zhou","year":"2013","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_192","unstructured":"Meng, G., Tang, X., Yang, Y., Benesch, M.G.K., Marshall, A., Murray, D., Hemmings, D.G., Wuest, F., McMullen, T.P.W., and Brindley, D.N. (2017). Gamma-radiation causes an inflammatory wound healing response in adipose tissue involving autotaxin and lysophosphatidate signaling. FASEB J."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Schleicher, S.M., Thotala, D.K., Linkous, A.G., Hu, R., Leahy, K.M., Yazlovitskaya, E.M., and Hallahan, D.E. (2011). Autotaxin and LPA receptors represent potential molecular targets for the radiosensitization of murine glioma through effects on tumor vasculature. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022182"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fonc.2013.00236","article-title":"Autotaxin inhibition with PF-8380 enhances the radiosensitivity of human and murine glioblastoma cell lines","volume":"3","author":"Bhave","year":"2013","journal-title":"Front. Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Harris, J.R. (2014). Fifty years of progress in radiation therapy for breast cancer. Am. Soc. Clin. Oncol. Educ. Book, 21\u201325.","DOI":"10.14694\/EdBook_AM.2014.34.21"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2011.04.084","article-title":"Blockade of lysophosphatidic acid receptors LPAR1\/3 ameliorates lung fibrosis induced by irradiation","volume":"409","author":"Gan","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_197","first-page":"1515","article-title":"Effects of lysophosphatidic acid and its receptors LPA(1\/3) on radiation pneumonitis","volume":"24","author":"Xue","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1021\/acs.jmedchem.7b00032","article-title":"Discovery of 2-[[2-ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methyli midazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a first-in-class autotaxin inhibitor undergoing clinical evaluation for the treatment of idiopathic pulmonary fibrosis","volume":"60","author":"Desroy","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.yexcr.2014.11.020","article-title":"Lysophospholipid receptors in drug discovery","volume":"333","author":"Kihara","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1742-2094-11-37","article-title":"Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes","volume":"11","author":"Crack","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbalip.2012.08.015","article-title":"Role of the autotaxin-lysophosphatidate axis in cancer resistance to chemotherapy and radiotherapy","volume":"1831","author":"Brindley","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"43543","DOI":"10.18632\/oncotarget.16672","article-title":"Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: A pivotal target to improve the radiotherapy therapeutic index","volume":"8","author":"Rancoule","year":"2017","journal-title":"Oncotarget"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.semradonc.2017.04.001","article-title":"Mechanisms of normal tissue injury from irradiation","volume":"27","author":"Citrin","year":"2017","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nrclinonc.2013.245","article-title":"Mitigating the toxic effects of anticancer immunotherapy","volume":"11","author":"Gangadhar","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Yang, L., Yu, H., Dong, S., Zhong, Y., and Hu, S. (2017). Recognizing and managing on toxicities in cancer immunotherapy. Tumour Biol., 39.","DOI":"10.1177\/1010428317694542"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/73\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:08Z","timestamp":1760194628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/73"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":205,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["cancers10030073"],"URL":"https:\/\/doi.org\/10.3390\/cancers10030073","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]}}}