{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T15:28:29Z","timestamp":1792337309087,"version":"4.4.0"},"reference-count":157,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Schweizerischer Nationalfonds zur F&amp;#x00F6;rderung der Wissenschaftlichen Forschung","award":["31003A_159824"],"award-info":[{"award-number":["31003A_159824"]}]},{"DOI":"10.13039\/501100004361","name":"Krebsliga Schweiz","doi-asserted-by":"publisher","award":["KFS 4400-02-2018"],"award-info":[{"award-number":["KFS 4400-02-2018"]}],"id":[{"id":"10.13039\/501100004361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","award":["FF18115"],"award-info":[{"award-number":["FF18115"]}],"id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK\u2013Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt\/\u03b2-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology. In this review, we summarize some of the most relevant interactions between FAK and Wnt in different cancers, address the current landscape of Wnt- and FAK-targeted therapies in different clinical trials, and discuss the rationale for targeting the FAK\u2013Wnt crosstalk, along with the possible translational implications.<\/jats:p>","DOI":"10.3390\/ijms21239107","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:26:12Z","timestamp":1606731972000},"page":"9107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-7029","authenticated-orcid":false,"given":"Janine","family":"W\u00f6rthm\u00fcller","sequence":"first","affiliation":[{"name":"Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9137-7695","authenticated-orcid":false,"given":"Curzio","family":"R\u00fcegg","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nrc3792","article-title":"FAK in cancer: Mechanistic findings and clinical applications","volume":"14","author":"Sulzmaier","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2014.10.001","article-title":"FAK signaling in human cancer as a target for therapeutics","volume":"146","author":"Lee","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1242\/jcs.045112","article-title":"Cellular functions of FAK kinases: Insight into molecular mechanisms and novel functions","volume":"123","author":"Schaller","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2741\/4236","article-title":"Targeting FAK in human cancer: From finding to first clinical trials","volume":"19","author":"Golubovskaya","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrd4233","article-title":"Can we safely target the WNT pathway?","volume":"13","author":"Kahn","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1101\/cshperspect.a011163","article-title":"Wnt signaling","volume":"4","author":"Nusse","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11912-019-0763-9","article-title":"Recent Development of Wnt Signaling Pathway Inhibitors for Cancer Therapeutics","volume":"21","author":"Harb","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.devcel.2011.11.006","article-title":"Crosstalk in Cellular Signaling: Background Noise or the Real Thing?","volume":"21","author":"Vert","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1038\/ncomms16009","article-title":"Crosstalk and the evolvability of intracellular communication","volume":"8","author":"Rowland","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1158\/1078-0432.CCR-09-3182","article-title":"Targeting multiple kinase pathways: A change in paradigm","volume":"16","author":"Gossage","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molcel.2007.11.031","article-title":"Nuclear FAK Promotes Cell Proliferation and Survival through FERM-Enhanced p53 Degradation","volume":"29","author":"Lim","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1023\/A:1023725029589","article-title":"FAK regulates biological processes important for the pathogenesis of cancer","volume":"22","author":"Schaller","year":"2003","journal-title":"Cancer Metastasis Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-4889(01)00123-9","article-title":"Biochemical signals and biological responses elicited by the focal adhesion kinase","volume":"1540","author":"Schaller","year":"2001","journal-title":"Biochim. Biophys. Acta (BBA) Bioenergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00303256","article-title":"Mapping of the focal adhesion kinase (Fadk) gene to mouse chromosome 15 and human chromosome 8","volume":"6","author":"Fiedorek","year":"1995","journal-title":"Mamm. Genome"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1073\/pnas.89.11.5192","article-title":"pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions","volume":"89","author":"Schaller","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1073\/pnas.89.18.8487","article-title":"Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin","volume":"89","author":"Hanks","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1006\/bbrc.1993.1022","article-title":"Expression of an N-Terminally Truncated Form of Human Focal Adhesion Kinase in Brain","volume":"190","author":"Andre","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0378-1119(95)00153-W","article-title":"Cloning of a Xenopus laevis cDNA encoding focal adhesion kinase (FAK) and expression during early development","volume":"160","author":"Zhang","year":"1995","journal-title":"Gene"},{"key":"ref_19","first-page":"1680","article-title":"Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src","volume":"14","author":"Schaller","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10678","DOI":"10.1073\/pnas.92.23.10678","article-title":"Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas","volume":"92","author":"Polte","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26329","DOI":"10.1074\/jbc.271.42.26329","article-title":"Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase","volume":"271","author":"Chen","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ceb.2006.08.011","article-title":"Integrin-regulated FAK-Src signaling in normal and cancer cells","volume":"18","author":"Mitra","year":"2006","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ceb.2005.08.007","article-title":"Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition","volume":"17","author":"Avizienyte","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_24","first-page":"2752","article-title":"Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors","volume":"55","author":"Owens","year":"1995","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/BF02409059","article-title":"Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer","volume":"3","author":"Owens","year":"1996","journal-title":"Ann. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/(SICI)1097-0215(19961009)68:2<169::AID-IJC4>3.0.CO;2-W","article-title":"Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma","volume":"68","author":"Tremblay","year":"1996","journal-title":"Int. J. Cancer"},{"key":"ref_27","first-page":"215","article-title":"Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: Immunohistochemistry and real-time PCR analyses","volume":"9","author":"Lark","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1002\/(SICI)1097-0142(19991015)86:6<1551::AID-CNCR23>3.0.CO;2-P","article-title":"Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma","volume":"86","author":"Judson","year":"1999","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36256","DOI":"10.18632\/oncotarget.26332","article-title":"Calretinin promotes invasiveness and EMT in malignant mesothelioma cells involving the activation of the FAK signaling pathway","volume":"9","author":"Blum","year":"2018","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10549-010-1150-2","article-title":"Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer","volume":"128","author":"Yom","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1158\/1078-0432.CCR-05-1583","article-title":"Overexpression of Focal Adhesion Kinase in Head and Neck Squamous Cell Carcinoma Is Independent of fak Gene Copy Number","volume":"12","author":"Canel","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21526","DOI":"10.1074\/jbc.M110.129999","article-title":"Knock-in mutation reveals an essential role for focal adhesion kinase activity in blood vessel morphogenesis and cell motility-polarity but not cell proliferation","volume":"285","author":"Lim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrm1549","article-title":"Focal adhesion kinase: In command and control of cell motility","volume":"6","author":"Mitra","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/embj.201386399","article-title":"FAK dimerization controls its kinase-dependent functions at focal adhesions","volume":"33","author":"Gervasi","year":"2014","journal-title":"EMBO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1242\/jcs.109.7.1787","article-title":"Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn","volume":"109","author":"Cary","year":"1996","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1242\/jcs.00373","article-title":"Focal adhesion kinase: The first ten years","volume":"116","author":"Parsons","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25008","DOI":"10.1074\/jbc.M414172200","article-title":"Direct Interaction of the N-terminal Domain of Focal Adhesion Kinase with the N-terminal Transactivation Domain of p53","volume":"280","author":"Golubovskaya","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-019-1265-1","article-title":"The roles of nuclear focal adhesion kinase (FAK) on Cancer: A focused review","volume":"38","author":"Zhou","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4161\/org.4.2.5851","article-title":"Wnt signal transduction pathways","volume":"4","author":"Komiya","year":"2008","journal-title":"Organogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/beta-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/path.1692","article-title":"Wnt signalling and the mechanistic basis of tumour development","volume":"205","author":"Ilyas","year":"2005","journal-title":"J. Pathol."},{"key":"ref_42","first-page":"392","article-title":"A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing","volume":"503","author":"Florian","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22429","DOI":"10.1074\/jbc.R600015200","article-title":"Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors","volume":"281","author":"Gordon","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/iub.559","article-title":"Protein kinase C in Wnt signaling: Implications in cancer initiation and progression","volume":"63","year":"2011","journal-title":"IUBMB Life"},{"key":"ref_45","first-page":"a008029","article-title":"Wnt Signaling in Skin Development, Homeostasis, and Disease","volume":"5","author":"Lim","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev.genet.42.110807.091432","article-title":"Planar Cell Polarity Signaling: From Fly Development to Human Disease","volume":"42","author":"Simons","year":"2008","journal-title":"Annu. Rev. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10439","DOI":"10.1158\/0008-5472.CAN-06-2359","article-title":"Expression of Wnt-5a Is Correlated with Aggressiveness of Gastric Cancer by Stimulating Cell Migration and Invasion","volume":"66","author":"Kurayoshi","year":"2006","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/path.4841","article-title":"Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer","volume":"241","author":"Corda","year":"2017","journal-title":"J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-25672-6","article-title":"Dramatic dysbalancing of the Wnt pathway in breast cancers","volume":"8","author":"Koval","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_50","first-page":"539","article-title":"Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice","volume":"377","author":"Furuta","year":"1995","journal-title":"Nat. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1083\/jcb.200411155","article-title":"Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis","volume":"169","author":"Shen","year":"2005","journal-title":"J Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nn1329","article-title":"Activation of FAK and Src are receptor-proximal events required for netrin signaling","volume":"7","author":"Li","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_53","first-page":"1039","article-title":"The role of focal adhesion kinase in early development","volume":"25","author":"Chatzizacharias","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"dev146589","DOI":"10.1242\/dev.146589","article-title":"Wnt signaling in development and tissue homeostasis","volume":"145","author":"Steinhart","year":"2018","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1248012","DOI":"10.1126\/science.1248012","article-title":"Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control","volume":"346","author":"Clevers","year":"2014","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2174\/187152011796817673","article-title":"FAK and WNT Signaling: The Meeting of Two Pathways in Cancer and Development","volume":"11","author":"Fonar","year":"2011","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1534-5807(02)00142-9","article-title":"DWnt4 Regulates Cell Movement and Focal Adhesion Kinase during Drosophila Ovarian Morphogenesis","volume":"2","author":"Cohen","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1091\/mbc.e10-12-0932","article-title":"Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate","volume":"22","author":"Fonar","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1002\/jbmr.2908","article-title":"FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling","volume":"31","author":"Sun","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1080\/21691401.2019.1631838","article-title":"FAK mediates BMP9-induced osteogenic differentiation via Wnt and MAPK signaling pathway in synovial mesenchymal stem cells","volume":"47","author":"Zheng","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.biopha.2018.04.185","article-title":"FAK and BMP-9 synergistically trigger osteogenic differentiation and bone formation of adipose derived stem cells through enhancing Wnt-beta-catenin signaling","volume":"105","author":"Yuan","year":"2018","journal-title":"Biomed. Pharm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.devcel.2010.07.015","article-title":"Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt\/c-Myc signaling","volume":"19","author":"Ashton","year":"2010","journal-title":"Dev. Cell."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1096\/fj.201801176R","article-title":"Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis","volume":"33","author":"Oshima","year":"2019","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/carcin\/bgs284","article-title":"Focal adhesion kinase is required for beta-catenin-induced mobilization of epidermal stem cells","volume":"33","author":"Ridgway","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_65","first-page":"106","article-title":"Cancer Statistics, 2006","volume":"56","author":"Jemal","year":"2006","journal-title":"CA: A Cancer J. Clin."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Network (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487, 330\u2013337.","DOI":"10.1038\/nature11252"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1073\/pnas.0811902106","article-title":"Activated Wnt\/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model","volume":"106","author":"Chien","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-Catenin Signaling, Disease, and Emerging Therapeutic Modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-1-4419-1145-2_8","article-title":"APC and Its Modifiers in Colon Cancer","volume":"656","author":"Kwong","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1038\/s41598-020-59899-z","article-title":"APC controls Wnt-induced beta-catenin destruction complex recruitment in human colonocytes","volume":"10","author":"Parker","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.cell.2012.05.002","article-title":"Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex","volume":"149","author":"Li","year":"2012","journal-title":"Cell"},{"key":"ref_73","first-page":"731","article-title":"Glycogen Synthase Kinase 3beta Is Positively Regulated by Protein Kinase Czeta-Mediated Phosphorylation Induced by Wnt Agonists","volume":"36","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e10072","DOI":"10.7554\/eLife.10072","article-title":"FAK\/PYK2 promotes the Wnt\/beta-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3beta","volume":"4","author":"Gao","year":"2015","journal-title":"Elife"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1158\/1535-7163.MCT-17-0561","article-title":"Wnt\/beta-Catenin Pathway Activation Mediates Adaptive Resistance to BRAF Inhibition in Colorectal Cancer","volume":"17","author":"Chen","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"57","DOI":"10.18632\/oncoscience.401","article-title":"Targeting parallel bypass signaling to combat adaptive resistance to BRAF inhibition in colorectal Cancer","volume":"5","author":"Gao","year":"2018","journal-title":"Oncoscience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"584","DOI":"10.2174\/1871520611313040008","article-title":"FAK and HAS inhibition synergistically decrease colon cancer cell viability and affect expression of critical genes","volume":"13","author":"Heffler","year":"2013","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1002\/1521-4141(200105)31:5<1417::AID-IMMU1417>3.0.CO;2-C","article-title":"Focal adhesion kinase regulates beta1 integrin-dependent T cell migration through an HEF1 effector pathway","volume":"31","author":"Salmen","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1038\/sj.onc.1209199","article-title":"HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells","volume":"25","author":"Natarajan","year":"2005","journal-title":"Oncogene"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1038\/onc.2010.632","article-title":"HEF1, a novel target of Wnt signaling, promotes colonic cell migration and cancer progression","volume":"30","author":"Li","year":"2011","journal-title":"Oncogene"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4161\/cc.10.2.14350","article-title":"A FAK-PI-3K-mTOR axis is required for Wnt-Myc driven intestinal regeneration and tumorigenesis","volume":"10","author":"Morton","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nrc1647","article-title":"The role of focal-adhesion kinase in cancer\u2014A new therapeutic opportunity","volume":"5","author":"McLean","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11864-008-0067-z","article-title":"Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis","volume":"9","author":"Yang","year":"2008","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"W\u00f6rthm\u00fcller, J., Salicio, V., Oberson, A., Blum, W., and Schwaller, B. (2019). Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215391"},{"key":"ref_85","first-page":"4547","article-title":"Wnt pathway activation in mesothelioma: Evidence of Dishevelled overexpression and transcriptional activity of beta-catenin","volume":"63","author":"Uematsu","year":"2003","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6672","DOI":"10.1038\/sj.onc.1207881","article-title":"Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma","volume":"23","author":"Lee","year":"2004","journal-title":"Oncogene"},{"key":"ref_87","first-page":"446","article-title":"Attenuation of Focal Adhesion Kinase Reduces Lipopolysaccharide-Induced Inflammation Injury through Inactivation of the Wnt and NF-kappaB Pathways in A549 Cells","volume":"82","author":"Bai","year":"2017","journal-title":"Biochemistry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11010-015-2331-4","article-title":"Maclurin suppresses migration and invasion of human non-small-cell lung cancer cells via anti-oxidative activity and inhibition of the Src\/FAK-ERK-beta-catenin pathway","volume":"402","author":"Ku","year":"2015","journal-title":"Mol. Cel. Biochem."},{"key":"ref_89","first-page":"1","article-title":"Antimigratory Effects of the Methanol Extract from Momordica charantia on Human Lung Adenocarcinoma CL1 Cells","volume":"2012","author":"Hsu","year":"2012","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1620\/tjem.223.45","article-title":"Blockade of the Wnt\/beta-catenin pathway attenuates bleomycin-induced pulmonary fibrosis","volume":"223","author":"Kim","year":"2011","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0002-9440(10)62260-2","article-title":"Modulation of Prosurvival Signaling in Fibroblasts by a Protein Kinase Inhibitor Protects against Fibrotic Tissue Injury","volume":"166","author":"Vittal","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_92","first-page":"8","article-title":"FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy","volume":"8","author":"Ozmadenci","year":"2019","journal-title":"eLife"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ygyno.2005.11.017","article-title":"Acquisition of chemoresistance following discontinuous exposures to cisplatin is associated in ovarian carcinoma cells with progressive alteration of FAK, ERK and p38 activation in response to treatment","volume":"101","author":"Villedieu","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.biopha.2016.03.053","article-title":"Extracellular matrix protein ITGBL1 promotes ovarian cancer cell migration and adhesion through Wnt\/PCP signaling and FAK\/SRC pathway","volume":"81","author":"Sun","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1158\/0008-5472.CAN-15-0240","article-title":"ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFbeta Signaling Pathway","volume":"75","author":"Li","year":"2015","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/wound.2012.0363","article-title":"Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts","volume":"2","author":"Leask","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.biopha.2018.05.033","article-title":"ITGBL1 promotes migration, invasion and predicts a poor prognosis in colorectal cancer","volume":"104","author":"Qiu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.biocel.2015.12.004","article-title":"Twist induces epithelial-mesenchymal transition and cell motility in breast cancer via ITGB1-FAK\/ILK signaling axis and its associated downstream network","volume":"71","author":"Yang","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Yeh, Y.C., Lin, H.H., and Tang, M.J. (2012). A tale of two collagen receptors, integrin beta1 and discoidin domain receptor 1, in epithelial cell differentiation. Am. J. Physiol. Cell Physiol., C1207\u2013C1217.","DOI":"10.1152\/ajpcell.00253.2012"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.2174\/138945010792006780","article-title":"A Wnt-ow of opportunity: Targeting the Wnt\/beta-catenin pathway in breast cancer","volume":"11","author":"Prosperi","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Prosperi, J.R., Khramtsov, A.I., Khramtsova, G.F., and Goss, K.H. (2011). Apc mutation enhances PyMT-induced mammary tumorigenesis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029339"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/stem.1843","article-title":"Focal Adhesion Kinase and Wnt Signaling Regulate Human Ductal Carcinoma In Situ Stem Cell Activity and Response to Radiotherapy","volume":"33","author":"Williams","year":"2015","journal-title":"Stem Cells"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"51733","DOI":"10.18632\/oncotarget.18517","article-title":"Inhibition of FAK kinase activity preferentially targets cancer stem cells","volume":"8","author":"Kolev","year":"2017","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/hep.27402","article-title":"FAK is required for c-Met\/beta-catenin-driven hepatocarcinogenesis","volume":"61","author":"Shang","year":"2015","journal-title":"Hepatology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/hep.30707","article-title":"Focal Adhesion Kinase and beta-Catenin Cooperate to Induce Hepatocellular Carcinoma","volume":"70","author":"Shang","year":"2019","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2019.02.040","article-title":"PTK2 promotes cancer stem cell traits in hepatocellular carcinoma by activating Wnt\/beta-catenin signaling","volume":"450","author":"Fan","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_107","first-page":"348","article-title":"VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression","volume":"26","author":"Carracedo","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1002\/stem.1157","article-title":"Focal Adhesion Kinase Splice Variants Maintain Primitive Acute Myeloid Leukemia Cells Through Altered Wnt Signaling","volume":"30","author":"Despeaux","year":"2012","journal-title":"Stem Cells"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1166\/jbn.2019.2804","article-title":"Golgi Phosphoprotein 3 Promotes Malignant Phenotypes via FAK\/Raf\/MEK and Wnt\/beta-Catenin Signaling Pathways in Human Renal Cell Carcinoma","volume":"15","author":"He","year":"2019","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7589","DOI":"10.18632\/oncotarget.2280","article-title":"Osteoblast-derived WNT-induced secreted protein 1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126","volume":"5","author":"Tai","year":"2014","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s12038-017-9700-y","article-title":"Knockdown of Cripto-1 inhibits the proliferation, migration, invasion, and angiogenesis in prostate carcinoma cells","volume":"42","author":"Wu","year":"2017","journal-title":"J. Biosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev-med-070909-182917","article-title":"Mechanisms of Endocrine Resistance in Breast Cancer","volume":"62","author":"Osborne","year":"2011","journal-title":"Annu. Rev. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/1758834015614530","article-title":"Pharmacologic resistance in colorectal cancer: A review","volume":"8","author":"Hammond","year":"2015","journal-title":"Ther. Adv. Med Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.critrevonc.2016.08.011","article-title":"The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?","volume":"107","author":"Bronte","year":"2016","journal-title":"Crit. Rev. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1158\/0008-5472.CAN-16-0097","article-title":"Quantification of Pathway Cross-talk Reveals Novel Synergistic Drug Combinations for Breast Cancer","volume":"77","author":"Jaeger","year":"2016","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.semcancer.2015.03.001","article-title":"Broad targeting of resistance to apoptosis in cancer","volume":"35","author":"Mohammad","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"63995","DOI":"10.18632\/oncotarget.11745","article-title":"Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination","volume":"7","author":"Sun","year":"2016","journal-title":"Oncotarget"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.3389\/fimmu.2019.02854","article-title":"WNT Signaling in Tumors: The Way to Evade Drugs and Immunity","volume":"10","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_119","first-page":"w20129","article-title":"Targeting the Wnt signalling pathway in cancer: Prospects and perils","volume":"149","author":"Shaw","year":"2019","journal-title":"Swiss Med Wkly."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s12276-020-0380-6","article-title":"Wnt signaling in cancer: Therapeutic targeting of Wnt signaling beyond beta-catenin and the destruction complex","volume":"52","author":"Jung","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"11717","DOI":"10.1073\/pnas.1120068109","article-title":"Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors","volume":"109","author":"Gurney","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e1700090","DOI":"10.1126\/sciadv.1700090","article-title":"WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death","volume":"3","author":"Fischer","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1158\/1078-0432.CCR-17-2157","article-title":"A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors","volume":"23","author":"Jimeno","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10549-020-05817-w","article-title":"Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer","volume":"184","author":"Diamond","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41413-018-0017-8","article-title":"Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy","volume":"6","author":"Madan","year":"2018","journal-title":"Bone Res."},{"key":"ref_126","unstructured":"OncoMed Pharmaceuticals, Inc. (2020, November 23). Annual Report. Available online: https:\/\/sec.report\/Document\/1302573\/000156459019006795\/omed-10k_20181231.htm."},{"key":"ref_127","first-page":"2740","article-title":"A Formylated Hexapeptide Ligand Mimics the Ability of Wnt-5a to Impair Migration of Human Breast Epithelial Cells","volume":"281","author":"Leandersson","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1182\/bloodadvances.2019000757","article-title":"Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome","volume":"4","author":"Lee","year":"2020","journal-title":"Blood Adv."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.canlet.2019.09.009","article-title":"The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models","volume":"473","author":"Tam","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1101\/gad.10.24.3116","article-title":"The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing","volume":"10","author":"Kadowaki","year":"1996","journal-title":"Genes Dev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1111\/bph.13864","article-title":"Pharmacological interventions in the Wnt pathway: Inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors","volume":"174","author":"Zimmerli","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1517\/14728222.2014.906580","article-title":"The potential of targeting Wnt\/beta-catenin in colon cancer","volume":"18","author":"Sebio","year":"2014","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1158\/1078-0432.CCR-14-2021","article-title":"Molecular Pathways: Endothelial Cell FAK\u2014A Target for Cancer Treatment","volume":"22","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1093\/annonc\/mdw427","article-title":"A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors","volume":"27","author":"Soria","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/s41416-019-0452-3","article-title":"A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours","volume":"120","author":"Mak","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11523-018-00617-1","article-title":"Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies","volume":"14","author":"Steeghs","year":"2019","journal-title":"Target. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1200\/JCO.2011.38.9346","article-title":"Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors","volume":"30","author":"Infante","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/13543776.2018.1414183","article-title":"FAK inhibitors in Cancer, a patent review","volume":"28","author":"Lv","year":"2018","journal-title":"Expert Opin. Ther. Patents"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1007\/s10637-015-0282-y","article-title":"A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors","volume":"33","author":"Jones","year":"2015","journal-title":"Investig. New Drugs"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1007\/s00280-016-3010-1","article-title":"A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors","volume":"77","author":"Shimizu","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"237ra68","DOI":"10.1126\/scitranslmed.3008639","article-title":"Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship","volume":"6","author":"Shapiro","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.lungcan.2019.10.033","article-title":"Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer","volume":"139","author":"Gerber","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/13543784.2020.1740680","article-title":"FAK-targeted and combination therapies for the treatment of cancer: An overview of phase I and II clinical trials","volume":"29","author":"Mohanty","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.cell.2012.10.014","article-title":"A Missing Link in Genotype-Directed Cancer Therapy","volume":"151","author":"Bernards","year":"2012","journal-title":"Cell"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13045-016-0241-x","article-title":"Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia","volume":"9","author":"Shi","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"38978","DOI":"10.1074\/jbc.M205002200","article-title":"Dual inhibition of focal adhesion kinase and epidermal growth factor receptor pathways cooperatively induces death receptor-mediated apoptosis in human breast cancer cells","volume":"277","author":"Golubovskaya","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_147","first-page":"755","article-title":"Simultaneous inhibition of focal adhesion kinase and SRC enhances detachment and apoptosis in colon cancer cell lines","volume":"1","author":"Golubovskaya","year":"2003","journal-title":"Mol. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1126\/science.280.5369.1614","article-title":"Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN","volume":"280","author":"Tamura","year":"1998","journal-title":"Science"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fonc.2017.00170","article-title":"New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN\/Focal Adhesion Kinase Pathway","volume":"7","author":"Alfieri","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1097\/00000478-199609000-00001","article-title":"Calretinin: A Novel Immunocytochemical Marker for Mesothelioma","volume":"20","author":"Doglioni","year":"1996","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Tang, J., Karhinen, L., Xu, T., Szwajda, A., Yadav, B., Wennerberg, K., and Aittokallio, T. (2013). Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003226"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1159\/000315097","article-title":"Hyperactivity and Enhanced Curiosity of Mice Expressing PKB\/SGK-resistant Glycogen Synthase Kinase-3 (GSK-3)","volume":"25","author":"Ackermann","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Crampton, S.P., Wu, B., Park, E.J., Kim, J.H., Solomon, C., Waterman, M.L., and Hughes, C.C. (2009). Integration of the beta-catenin-dependent Wnt pathway with integrin signaling through the adaptor molecule Grb2. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007841"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1074\/jbc.274.1.129","article-title":"Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells","volume":"274","author":"Li","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ccr.2007.04.021","article-title":"Identification of the JNK Signaling Pathway as a Functional Target of the Tumor Suppressor PTEN","volume":"11","author":"Vivanco","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nbt.1549","article-title":"Synergistic drug combinations tend to improve therapeutically relevant selectivity","volume":"27","author":"Lehar","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.sbi.2016.07.020","article-title":"Two is better than one; toward a rational design of combinatorial therapy","volume":"41","author":"Chen","year":"2016","journal-title":"Curr. Opin. Struct. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:39:33Z","timestamp":1760179173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/9107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":157,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21239107"],"URL":"https:\/\/doi.org\/10.3390\/ijms21239107","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]}}}