{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T19:34:28Z","timestamp":1782243268762,"version":"3.54.5"},"reference-count":125,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["319412"],"award-info":[{"award-number":["319412"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hamilton Urologic Oncology Research Center (HUORC)","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Ontario Graduate Scholarships","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Research Institute of St Joe\u2019s Hamilton","award":["Studentship"],"award-info":[{"award-number":["Studentship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Even with recent progress, cancer remains the second leading cause of death, outlining a need to widen the current understanding on oncogenic factors. Accumulating evidence from recent years suggest Contactin 1 (CNTN1)\u2019s possession of multiple oncogenic activities in a variety of cancer types. CNTN1 is a cell adhesion molecule that is dysregulated in many human carcinomas and plays important roles in cancer progression and metastases. Abnormalities in CNTN1 expression associate with cancer progression and poor prognosis. Mechanistically, CNTN1 functions in various signaling pathways frequently altered in cancer, such as the vascular endothelial growth factor C (VEGFC)-VEGF receptor 3 (VEFGR3)\/fms-related tyrosine kinase 4 (Flt4) axis, phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (AKT), Notch signaling pathway and epithelial-mesenchymal transition (EMT) process. These oncogenic events are resulted via interactions between tumor and stroma, which can be contributed by CNTN1, an adhesion protein. CNTN1 expression in breast cancer correlates with the expression of genes functioning in cancer-stroma interactions and skeletal system development. Evidence supports that CNTN1 promotes cancer-stromal interaction, resulting in activation of a complex network required for cancer progression and metastasis (bone metastasis for breast cancer). CNTN1 inhibitions has been proven to be effective in experimental models to reduce oncogenesis. In this paper, we will review CNTN1\u2032s alterations in cancer, its main biochemical mechanisms and interactions with its relevant cancer pathways.<\/jats:p>","DOI":"10.3390\/genes11080874","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T07:45:57Z","timestamp":1596440757000},"page":"874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Contactin 1: An Important and Emerging Oncogenic Protein Promoting Cancer Progression and Metastasis"],"prefix":"10.3390","volume":"11","author":[{"given":"Yan","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada"},{"name":"The Research Institute of St Joe\u2019s Hamilton, St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"},{"name":"Urological Cancer Center for Research and Innovation (UCCRI), St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taosha","family":"Li","sequence":"additional","affiliation":[{"name":"Life-Tech Industry Alliance, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada"},{"name":"The Research Institute of St Joe\u2019s Hamilton, St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"},{"name":"Urological Cancer Center for Research and Innovation (UCCRI), St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"},{"name":"Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Major","sequence":"additional","affiliation":[{"name":"Department of Oncology, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada"},{"name":"The Research Institute of St Joe\u2019s Hamilton, St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"},{"name":"Urological Cancer Center for Research and Innovation (UCCRI), St. Joseph\u2019s Hospital, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.3109\/07357900902769749","article-title":"Cell Adhesion Molecules: Role and clinical significance in cancer","volume":"27","author":"Makrilia","year":"2009","journal-title":"Cancer Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1196\/annals.1294.006","article-title":"Multitasking in tumor progression: Signaling functions of cell adhesion molecules","volume":"1014","author":"Cavallaro","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nrc1886","article-title":"Metastasis: A question of life or death","volume":"6","author":"Mehlen","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.2174\/138161206777947759","article-title":"Adhesion molecules as targets for the treatment of neoplastic diseases","volume":"12","author":"Syrigos","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1096\/fasebj.3.5.2522071","article-title":"Glycosyl-phosphatidylinositol: A versatile anchor for cell surface proteins 1","volume":"3","author":"Low","year":"1989","journal-title":"FASEB J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9707","DOI":"10.3748\/wjg.v21.i33.9707","article-title":"Contactin 1: A potential therapeutic target and biomarker in gastric cancer","volume":"21","author":"Chen","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_7","first-page":"12473","article-title":"Contactin 1 as a potential biomarker promotes cell proliferation and invasion in thyroid cancer","volume":"8","author":"Shi","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.23736\/S0026-4806.16.04683-8","article-title":"Contactin-1: A promising progression biomarker and therapeutic target of carcinoma","volume":"108","author":"Zhang","year":"2017","journal-title":"Minerva Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mcn.2016.11.006","article-title":"The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders","volume":"81","author":"Gennarini","year":"2017","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4161\/cam.3.1.7462","article-title":"The mouse F3\/contactin glycoprotein","volume":"3","author":"Bizzoca","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ydbio.2012.02.011","article-title":"F3\/Contactin acts as a modulator of neurogenesis during cerebral cortex development","volume":"365","author":"Bizzocaa","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_12","first-page":"E394","article-title":"Contactin-1 regulates myelination and nodal\/paranodal domain organization in the central nervous system","volume":"111","author":"Berglund","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1017\/S1740925X09990111","article-title":"Modulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules","volume":"4","author":"Dityatev","year":"2008","journal-title":"Neuron Glia Boil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0092-8674(03)00810-9","article-title":"F3\/contactin acts as a functional ligand for notch during oligodendrocyte maturation","volume":"115","author":"Hu","year":"2003","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0896-6273(00)81126-5","article-title":"Ataxia and abnormal cerebellar microorganization in mice with ablated contactin gene expression","volume":"24","author":"Berglund","year":"1999","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.4161\/cam.3.1.7764","article-title":"Contactins: Emerging key roles in the development and function of the nervous system","volume":"3","author":"Shimoda","year":"2009","journal-title":"Cell Adh. Migr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1073\/pnas.0911235107","article-title":"The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules","volume":"107","author":"Bouyain","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0092-8674(95)90312-7","article-title":"The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin","volume":"82","author":"Peles","year":"1995","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1083\/jcb.136.4.907","article-title":"Induction of neurite outgrowth through contactin and nr-CAM by extracellular regions of glial receptor tyrosine phosphatase \u03b2","volume":"136","author":"Sakurai","year":"1997","journal-title":"J. Cell Boil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/j.1365-2826.2007.01597.x","article-title":"A contactin\u2013receptor-like protein tyrosine phosphatase \u03b2 complex mediates adhesive communication between astroglial cells and gonadotrophin-releasing hormone neurones","volume":"19","author":"Parent","year":"2007","journal-title":"J. Neuroendocr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17498","DOI":"10.1073\/pnas.1108774108","article-title":"A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells","volume":"108","author":"Lamprianou","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1159\/000090750","article-title":"Cross-talk between F3\/contactin and notch at axoglial interface: A role in oligodendrocyte development","volume":"28","author":"Hu","year":"2006","journal-title":"Dev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/367572a0","article-title":"Initial events of myelination involve Fyn tyrosine kinase signalling","volume":"367","author":"Umemori","year":"1994","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.mcn.2011.12.002","article-title":"The role of nr. CAM in neural development and disorders\u2014Beyond a simple glue in the brain","volume":"49","author":"Sakurai","year":"2012","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0896-6273(93)90243-K","article-title":"The F3\/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160\/180","volume":"10","author":"Pesheva","year":"1993","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fnmol.2018.00422","article-title":"Contactin-1\/F3 regulates neuronal migration and morphogenesis through modulating rhoa activity","volume":"11","author":"Chen","year":"2018","journal-title":"Front Mol. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0304-3940(98)00179-7","article-title":"Age-related decline of F3\/contactin in rat hippocampus","volume":"245","author":"Shimazaki","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.ajhg.2008.10.022","article-title":"Mutations in Contactin-1, a Neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy","volume":"83","author":"Compton","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0248-4900(02)00006-0","article-title":"F3\/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination","volume":"94","author":"Falk","year":"2002","journal-title":"Boil. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1242\/jcs.115.2.283","article-title":"NCAM regulates cell motility","volume":"115","author":"Prag","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1038\/emboj.2008.178","article-title":"NCAM-induced focal adhesion assembly: A functional switch upon loss of E-cadherin","volume":"27","author":"Lehembre","year":"2008","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/15419060214520","article-title":"Expression Level of Neural Cell Adhesion Molecule (NCAM) Inversely Correlates with the Ability of Neuroblastoma Cells to Adhere to Endothelium In Vitro","volume":"9","author":"Blaheta","year":"2002","journal-title":"Cell Commun. Adhes."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Blaheta, R.A., Daher, F.H., Michaelis, M., Hasenberg, C., Weich, E.M., Jonas, D., Kotchetkov, R., Doerr, H.W., and Cinatl, J. (2006). Chemoresistance induces enhanced adhesion and transendothelial penetration of neuroblastoma cells by down-regulating NCAM surface expression. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-294"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2559.2004.01834.x","article-title":"Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis","volume":"44","author":"Martin","year":"2004","journal-title":"Histopathology"},{"key":"ref_35","first-page":"1234","article-title":"The phenotype of normal, reactive and malignant plasma cells. Identification of \u201cmany and multiple myelomas\u201d and of new targets for myeloma therapy","volume":"91","author":"Bataille","year":"2006","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/sj.leu.2402174","article-title":"CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis","volume":"15","author":"Raspadori","year":"2001","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajh.20739","article-title":"Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation","volume":"82","author":"Yang","year":"2007","journal-title":"Am. J. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0304-3835(98)00359-0","article-title":"Expression of highly polysialylated neural cell adhesion molecule in pancreatic cancer neural invasive lesion","volume":"137","author":"Kameda","year":"1999","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/00006676-200103000-00003","article-title":"Expression of Neural Cell Adhesion Molecule in Pancreatic Cancer","volume":"22","author":"Tezel","year":"2001","journal-title":"Pancreas"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2739\/kurumemedj.53.59","article-title":"CD56 (NCAM) expression in pancreatic carcinoma and the surrounding pancreatic tissue","volume":"53","author":"Naito","year":"2006","journal-title":"Kurume Med. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/jso.1065","article-title":"Expression of neural cell adhesion molecules (polysialylated form of neural cell adhesion molecule and L1-cell adhesion molecule) on resected small cell lung cancer specimens: In relation to proliferation state","volume":"77","author":"Miyahara","year":"2001","journal-title":"J. Surg. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1006\/geno.1994.1316","article-title":"Molecular Cloning and in Situ Localization of the Human Contactin Gene (CNTN1) on Chromosome 12q11-q12","volume":"21","author":"Berglund","year":"1994","journal-title":"Genomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10385","DOI":"10.1093\/nar\/17.24.10385","article-title":"The human HOX gene family","volume":"17","author":"Acampora","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1172\/JCI113548","article-title":"Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa","volume":"81","author":"Sosnoski","year":"1988","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1601-5223.1989.tb00437.x","article-title":"In situ hybridization localizes the human type II alpha 1 collagen gene (COL2A1) to 12q13","volume":"110","author":"Arheden","year":"2008","journal-title":"Hereditas"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9193","DOI":"10.1073\/pnas.86.23.9193","article-title":"Isolation and characterization of ERBB3, a third member of the ERBB\/epidermal growth factor receptor family: Evidence for overexpression in a subset of human mammary tumors","volume":"86","author":"Kraus","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000132513","article-title":"Chromosome localization of the human oncogene INT1 to 12q13 by in situ hybridization","volume":"47","author":"Arheden","year":"1988","journal-title":"Cytogenet Cell Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc2748","article-title":"Integrins in cancer: Biological implications and therapeutic opportunities","volume":"10","author":"Desgrosellier","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/ajmg.1320310306","article-title":"Fragile site in chromosome 12 in a patient with two miscarriages","volume":"31","author":"Stetten","year":"1988","journal-title":"Am. J. Med Genet."},{"key":"ref_50","unstructured":"Mitelman, F. (1991). Catalog of Chromosome Abberrations in Cancer, Wiley-Liss. [4th ed.]."},{"key":"ref_51","first-page":"731","article-title":"Amplification at 12q13\u201314 in human malignant gliomas is frequently accompanied by loss of heterozygosity at loci proximal and distal to the amplification site","volume":"55","author":"Reifenberger","year":"1995","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/gcc.1113","article-title":"Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults","volume":"31","author":"Warr","year":"2001","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ccr.2006.02.018","article-title":"The VEGF-C\/Flt-4 axis promotes invasion and metastasis of cancer cells","volume":"9","author":"Su","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_54","first-page":"2046","article-title":"VEGF-C\/Flt-4 axis in tumor cells contributes to the progression of oral squamous cell carcinoma via upregulating VEGF-C itself and contactin-1 in an autocrine manner","volume":"8","author":"Shigetomi","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cca.2016.08.008","article-title":"Pathway-related molecules of VEGFC\/D-VEGFR3\/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis","volume":"461","author":"Wang","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.cbi.2008.10.042","article-title":"4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) enhances invasiveness of lung cancer cells by up-regulating contactin-1 via the \u03b17 nicotinic acetylcholine receptor\/ERK signaling pathway","volume":"179","author":"Hung","year":"2009","journal-title":"Chem. Interact."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12030","DOI":"10.1038\/s41598-019-48476-8","article-title":"Contactin 1 modulates pegylated arginase resistance in small cell lung cancer through induction of epithelial-mesenchymal transition","volume":"9","author":"Xu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yan, J., Wong, N., Hung, C.L., Chen, W.X.-Y., and Tang, D. (2013). Contactin-1 reduces e-cadherin expression via activating akt in lung cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065463"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1159\/000480473","article-title":"CNTN-1 enhances chemoresistance in human lung adenocarcinoma through induction of epithelial-mesenchymal transition by targeting the PI3K\/Akt pathway","volume":"43","author":"Zhang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_60","first-page":"1","article-title":"Expression and significances of contactin-1 in human gastric cancer","volume":"2013","author":"Yu","year":"2013","journal-title":"Gastroenterol. Res. Pr."},{"key":"ref_61","first-page":"7082408","article-title":"Identification and validation of an individualized emt-related prognostic risk score formula in gastric adenocarcinoma patients","volume":"2020","author":"Zhang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3471","DOI":"10.1111\/cas.13782","article-title":"Recombinant human arginase induces apoptosis through oxidative stress and cell cycle arrest in small cell lung cancer","volume":"109","author":"Xu","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_63","first-page":"1611","article-title":"Upregulation of contactin-1 expression promotes prostate cancer progression","volume":"19","author":"Wang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1158\/0008-5472.CAN-15-1898","article-title":"Neural cell adhesion protein CNTN1 promotes the metastatic progression of prostate cancer","volume":"76","author":"Yan","year":"2016","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.7314\/APJCP.2014.15.5.1925","article-title":"Comprehensive analysis of vascular endothelial growth factor-c related factors in stomach cancer","volume":"15","author":"Liu","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cyto.2011.03.008","article-title":"VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression","volume":"55","author":"Liu","year":"2011","journal-title":"Cytokine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.foodchem.2012.10.038","article-title":"Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-\u03b2 activation to enhance protein degradation and attenuate nuclear translocation of \u03b2-catenin","volume":"138","author":"Tsai","year":"2013","journal-title":"Food Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2147\/OTT.S97367","article-title":"Expression and prognostic significance of contactin 1 in human hepatocellular carcinoma","volume":"9","author":"Li","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/glia.20254","article-title":"Contactin is expressed in human astrocytic gliomas and mediates repulsive effects","volume":"53","author":"Eckerich","year":"2005","journal-title":"Glia"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/jjco\/hys066","article-title":"Contactin-1 (CNTN-1) Overexpression is Correlated with Advanced Clinical Stage and Lymph Node Metastasis in Oesophageal Squamous Cell Carcinomas","volume":"42","author":"Liu","year":"2012","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_71","first-page":"265","article-title":"Contactin 1 (CNTN1) expression associates with regional lymph node metastasis and is a novel predictor of prognosis in patients with oral squamous cell carcinoma","volume":"6","author":"Wu","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.biopha.2014.11.004","article-title":"Increased sensitivity of human lung adenocarcinoma cells to cisplatin associated with downregulated contactin-1","volume":"71","author":"Zhang","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chen, B., Zhang, Y., Li, C., Xu, P., Gao, Y., and Xu, Y. (2020). CNTN-1 promotes docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K\/Akt signaling pathway in prostate cancer. Arch. Med. Sci.","DOI":"10.5114\/aoms.2020.92939"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1158\/1078-0432.584.11.2","article-title":"Stage-specific characterization of the vascular endothelial growth factor axis in prostate cancer: Expression of lymphangiogenic markers is associated with advanced-stage disease","volume":"11","author":"Kaushal","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_75","first-page":"727","article-title":"Clinical significance of co-expression of VEGF-C and VEGFR-3 in non-small cell lung cancer","volume":"116","author":"Li","year":"2003","journal-title":"Chin. Med J."},{"key":"ref_76","first-page":"1463","article-title":"Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma","volume":"22","author":"Witte","year":"2002","journal-title":"Anticancer. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/hed.10235","article-title":"Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck","volume":"25","author":"Neuchrist","year":"2003","journal-title":"Head Neck"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/path.1467","article-title":"Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis","volume":"201","author":"Steele","year":"2003","journal-title":"J. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s11684-018-0656-6","article-title":"Epithelial-to-mesenchymal transition in cancer: Complexity and opportunities","volume":"12","author":"Zhang","year":"2018","journal-title":"Front. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000337106","article-title":"Epithelial-mesenchymal transition: A hallmark in metastasis formation linking circulating tumor cells and cancer stem cells","volume":"79","author":"Ksiazkiewicz","year":"2012","journal-title":"Pathobiolohy"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Boil."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/onc.2011.324","article-title":"PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma","volume":"31","author":"Molina","year":"2011","journal-title":"Oncogene"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nm.4409","article-title":"Cancer stem cells revisited","volume":"23","author":"Batlle","year":"2017","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"319","DOI":"10.5483\/BMBRep.2018.51.7.112","article-title":"Cancer stem cell metabolism: Target for cancer therapy","volume":"51","author":"Chae","year":"2018","journal-title":"BMB Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5483\/BMBRep.2017.50.3.222","article-title":"Cancer stem cell heterogeneity: Origin and new perspectives on CSC targeting","volume":"50","author":"Eun","year":"2017","journal-title":"BMB Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/pros.21473","article-title":"Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases","volume":"72","author":"Colombel","year":"2011","journal-title":"Prostate"},{"key":"ref_87","first-page":"274","article-title":"Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity","volume":"15","author":"Wang","year":"2013","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, N., He, S., Geng, J., Song, Z.-J., Han, P.-H., Qin, J., Zhao, Z., Song, Y.-C., Wang, H.-X., and Dang, C.-X. (2018). Overexpression of Contactin 1 promotes growth, migration and invasion in Hs578T breast cancer cells. BMC Cell Boil., 19.","DOI":"10.1186\/s12860-018-0154-3"},{"key":"ref_89","first-page":"765","article-title":"bc-GenExMiner: An easy-to-use online platform for gene prognostic analyses in breast cancer","volume":"131","author":"Campone","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_90","first-page":"bas060","article-title":"bc-GenExMiner 3.0: New mining module computes breast cancer gene expression correlation analyses","volume":"2013","author":"Campion","year":"2013","journal-title":"Database"},{"key":"ref_91","unstructured":"(2020, June 15). Breast Cancer Gene-Expression Miner v4.5. Available online: http:\/\/bcgenex.ico.unicancer.fr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10869","DOI":"10.1073\/pnas.191367098","article-title":"Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications","volume":"98","author":"Perou","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Haakensen, V.D., Lingj\u00e6rde, O.C., L\u00fcders, T., Riis, M.L., Prat, A., Troester, M.A., Holmen, M.M., Frantzen, J.O., Romundstad, L., and Navjord, D. (2011). Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features. BMC Med Genom., 4.","DOI":"10.1186\/1755-8794-4-77"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"490","DOI":"10.5858\/arpa.2016-0288-SA","article-title":"New developments in breast cancer and their impact on daily practice in pathology","volume":"141","author":"Li","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5306\/wjco.v5.i3.412","article-title":"Biological subtypes of breast cancer: Prognostic and therapeutic implications","volume":"5","author":"Yersal","year":"2014","journal-title":"World J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00109-015-1329-4","article-title":"Bone metastasis and the metastatic niche","volume":"93","author":"Ren","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"a031252","DOI":"10.1101\/cshperspect.a031252","article-title":"The Biology of Bone Metastasis","volume":"8","author":"Esposito","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_99","first-page":"12","article-title":"Diagnosis and treatment of prostate cancer","volume":"110","author":"Bagnall","year":"2014","journal-title":"Nurs. Times"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1089\/thy.2008.0362","article-title":"Distinct genetic alterations in the mitogen-activated protein kinase pathway dictate sensitivity of thyroid cancer cells to mitogen-activated protein kinase kinase 1\/2 inhibition","volume":"19","author":"Schweppe","year":"2009","journal-title":"Thyroid"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1210\/jc.2014-4153","article-title":"RET fusion as a novel driver of medullary thyroid carcinoma","volume":"100","author":"Grubbs","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4161\/cbt.12.5.16303","article-title":"Sunitinib inhibits papillary thyroid carcinoma with RET\/PTC rearrangement but not BRAF mutation","volume":"12","author":"Jeong","year":"2011","journal-title":"Cancer Boil. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Shiozaki, A., Shen-Tu, G., Bai, X., Iitaka, D., De Falco, V., Santoro, M., Keshavjee, S., and Liu, M. (2012). XB130 mediates cancer cell proliferation and survival through multiple signaling events downstream of akt. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043646"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"\u0141uczkowska, K., Rogi\u0144ska, D., Litwi\u0144ska, Z., Paczkowska, E., Schmidt, C.A., and Machali\u0144ski, B. (2020). Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA\u2013mRNA Interaction Involvement. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010350"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"110028","DOI":"10.1016\/j.biopha.2020.110028","article-title":"Molecule mechanisms of Ganoderma lucidum treated hepatocellular carcinoma based on the transcriptional profiles and miRNA-target network","volume":"125","author":"Tang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1600-0625.2011.01254.x","article-title":"Identification of new genes associated with melanoma","volume":"20","author":"Mauerer","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1158\/0008-5472.CAN-08-3767","article-title":"Active Notch1 confers a transformed phenotype to primary human melanocytes","volume":"69","author":"Pinnix","year":"2009","journal-title":"Cancer Res."},{"key":"ref_108","first-page":"1","article-title":"Notch signalling pathways and their importance in the treatment of cancers","volume":"18","author":"Das","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrclinonc.2015.61","article-title":"Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: Clinical update","volume":"12","author":"Takebe","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3389\/fonc.2018.00268","article-title":"Transgenic mouse models in cancer research","volume":"8","author":"Tratar","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1215\/15228517-2009-013","article-title":"Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array","volume":"11","author":"Nord","year":"2009","journal-title":"Neuro-Oncology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3892\/or.2015.3993","article-title":"Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data","volume":"34","author":"Mokhtar","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Luo, L., Tao, W., He, T., and Li, L.-Y. (2020). Prediction of potential prognostic biomarkers in metastatic prostate cancer based on a competing endogenous RNA regulatory network. Res. Sq., preprint.","DOI":"10.21203\/rs.3.rs-25943\/v1"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Cury, S.S., De Moraes, D., Freire, P.P., De Oliveira, G., Marques, D.V.P., Fernandez, G.J., Dal-Pai-Silva, M., Hasimoto, \u00c9.N., Reis, P., and Rogatto, S.R. (2019). Tumor transcriptome reveals high expression of IL-8 in non-small cell lung cancer patients with low pectoralis muscle area and reduced survival. Cancers, 11.","DOI":"10.3390\/cancers11091251"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3389\/fimmu.2019.01078","article-title":"Cell adhesion molecules and their roles and regulation in the immune and tumor microenvironment","volume":"10","author":"Asens","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/bjc.2011.183","article-title":"A randomised, phase II study of intetumumab, an anti-\u03b1v-integrin mAb, alone and with dacarbazine in stage IV melanoma","volume":"105","author":"Pavlick","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1158\/1078-0432.CCR-15-2512","article-title":"Differential effect on bone lesions of targeting integrins: Randomized phase II trial of abituzumab in patients with metastatic castration-resistant prostate cancer","volume":"22","author":"Hussain","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1084\/jem.20160831","article-title":"Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses","volume":"214","author":"Kwan","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1016\/j.biotechadv.2015.10.013","article-title":"Peptide vaccines in breast cancer: The immunological basis for clinical response","volume":"33","author":"Peres","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1158\/1078-0432.CCR-17-1839","article-title":"Identification of CRKII, CFL1, CNTN1, NME2, and TKT as novel and frequent T-cell targets in human IDH-mutant Gglioma","volume":"24","author":"Dettling","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Mei, W., Lin, X., Kapoor, A., Gu, Y., Zhao, K., and Tang, D. (2019). The contributions of prostate cancer stem cells in prostate cancer initiation and metastasis. Cancers, 11.","DOI":"10.3390\/cancers11040434"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.2741\/e561","article-title":"Cancer stem cells and niche mircoenvironments","volume":"4","author":"Nie","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1016\/j.biocel.2012.08.022","article-title":"Cancer stem cells","volume":"44","author":"Yu","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nrc3536","article-title":"The evolution of the cancer niche during multistage carcinogenesis","volume":"13","author":"Lyden","year":"2013","journal-title":"Nat. Rev. Cancer"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/8\/874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:28Z","timestamp":1760176408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/8\/874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":125,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["genes11080874"],"URL":"https:\/\/doi.org\/10.3390\/genes11080874","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]}}}