{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:19:53Z","timestamp":1792113593228,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1R01HL163192"],"award-info":[{"award-number":["1R01HL163192"]}]},{"name":"National Institutes of Health","award":["1R01HL149921"],"award-info":[{"award-number":["1R01HL149921"]}]},{"name":"National Institutes of Health","award":["1R01HL163635"],"award-info":[{"award-number":["1R01HL163635"]}]},{"name":"National Institutes of Health","award":["20TPA35490392"],"award-info":[{"award-number":["20TPA35490392"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["1R01HL163192"],"award-info":[{"award-number":["1R01HL163192"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["1R01HL149921"],"award-info":[{"award-number":["1R01HL149921"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["1R01HL163635"],"award-info":[{"award-number":["1R01HL163635"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20TPA35490392"],"award-info":[{"award-number":["20TPA35490392"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Vascular smooth muscle cells (VSMCs) are normally quiescent and non-migratory, regulating the contraction and relaxation of blood vessels to control the vascular tone. In response to arterial injury, these cells become active; they proliferate, secrete matrix proteins, and migrate, and thereby contribute importantly to the progression of several cardiovascular diseases. VSMC migration specifically supports atherosclerosis, restenosis after catheter-based intervention, transplant vasculopathy, and vascular remodeling during the formation of aneurysms. The atypical cadherin FAT1 is expressed robustly in activated VSMCs and promotes their migration. A positive role of FAT1 in the migration of other cell types, including neurons, fibroblasts, podocytes, and astrocyte progenitors, has also been described. In cancer biology, however, the effect of FAT1 on migration depends on the cancer type or context, as FAT1 either suppresses or enhances cancer cell migration and invasion. With this review, we describe what is known about FAT1\u2019s effects on cell migration as well as the factors that influence FAT1-dependent migration. In VSMCs, these factors include angiotensin II, which activates FAT1 expression and cell migration, and proteins of the Atrophin family: Atrophin-1 and the short isoform of Atrophin-2, which promote VSMC migration, and the long isoform of Atrophin-2, which exerts negative effects on FAT1-dependent VSMC migration.<\/jats:p>","DOI":"10.3390\/cells12121621","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T02:01:40Z","timestamp":1686708100000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The FAT1 Cadherin Drives Vascular Smooth Muscle Cell Migration"],"prefix":"10.3390","volume":"12","author":[{"given":"Dario F.","family":"Riascos-Bernal","sequence":"first","affiliation":[{"name":"Department of Medicine (Cardiology) and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6670-3838","authenticated-orcid":false,"given":"Gaia","family":"Ressa","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5419-7865","authenticated-orcid":false,"given":"Anish","family":"Korrapati","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4838-910X","authenticated-orcid":false,"given":"Nicholas E. S.","family":"Sibinga","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1146\/annurev-physiol-012110-142315","article-title":"Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease","volume":"74","author":"Alexander","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1093\/cvr\/cvab289","article-title":"PLX3397, a CSF1 receptor inhibitor, limits allotransplantation-induced vascular remodelling","volume":"118","author":"Almonte","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108157","DOI":"10.1016\/j.pharmthera.2022.108157","article-title":"Pharmacological prevention of intimal hyperplasia: A state-of-the-art review","volume":"235","author":"Melnik","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1161\/ATVBAHA.119.312787","article-title":"Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation","volume":"39","author":"Petsophonsakul","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10974-019-09531-z","article-title":"Emerging regulators of vascular smooth muscle cell migration","volume":"40","author":"Afewerki","year":"2019","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1161\/01.RES.0000258492.96097.47","article-title":"Mechanisms of vascular smooth muscle cell migration","volume":"100","author":"Gerthoffer","year":"2007","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1089\/ars.2009.2852","article-title":"Redox control of vascular smooth muscle migration","volume":"12","author":"Griendling","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1083\/jcb.200508121","article-title":"The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals","volume":"173","author":"Hou","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.yexcr.2005.03.006","article-title":"Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus","volume":"307","author":"Magg","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature20170","article-title":"Control of mitochondrial function and cell growth by the atypical cadherin Fat1","volume":"539","author":"Cao","year":"2016","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/gcc.20787","article-title":"Cadherin 13 in cancer","volume":"49","author":"Andreeva","year":"2010","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ydbio.2016.07.004","article-title":"The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice","volume":"417","author":"Glasco","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.canlet.2017.03.033","article-title":"FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK\/ERK signaling pathway in esophageal squamous cell cancer","volume":"397","author":"Hu","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41586-020-03046-1","article-title":"Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis","volume":"589","author":"Pastushenko","year":"2021","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1006\/geno.1995.9884","article-title":"Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule","volume":"30","author":"Dunne","year":"1995","journal-title":"Genomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24034","DOI":"10.1074\/jbc.M313878200","article-title":"The fat-like gene of Drosophila is the true orthologue of vertebrate fat cadherins and is involved in the formation of tubular organs","volume":"279","author":"Arias","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"905717","DOI":"10.3389\/fcvm.2022.905717","article-title":"The Atypical Cadherin FAT1 Limits Mitochondrial Respiration and Proliferation of Vascular Smooth Muscle Cells","volume":"9","author":"Maira","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0925-4773(98)00217-2","article-title":"Expression of the rat homologue of the Drosophila fat tumour suppressor gene","volume":"80","author":"Ponassi","year":"1999","journal-title":"Mech. Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2014.07.036","article-title":"The atypical cadherin fat directly regulates mitochondrial function and metabolic state","volume":"158","author":"Sing","year":"2014","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Caruso, N., Herberth, B., Bartoli, M., Puppo, F., Dumonceaux, J., Zimmermann, A., Denadai, S., Lebosse, M., Roche, S., and Geng, L. (2013). Deregulation of the protocadherin gene FAT1 alters muscle shapes: Implications for the pathogenesis of facioscapulohumeral dystrophy. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003550"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Helmbacher, F. (2018). Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2004734"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10822","DOI":"10.1038\/ncomms10822","article-title":"FAT1 mutations cause a glomerulotubular nephropathy","volume":"7","author":"Gee","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"dev192047","DOI":"10.1242\/dev.192047","article-title":"Astrocyte-intrinsic and -extrinsic Fat1 activities regulate astrocyte development and angiogenesis in the retina","volume":"149","author":"Helmbacher","year":"2022","journal-title":"Development"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1038\/sj.emboj.7600380","article-title":"Protocadherin FAT1 binds Ena\/VASP proteins and is necessary for actin dynamics and cell polarization","volume":"23","author":"Moeller","year":"2004","journal-title":"Embo. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1083\/jcb.200403006","article-title":"Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact","volume":"165","author":"Tanoue","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_27","first-page":"2781","article-title":"Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development","volume":"142","author":"Badouel","year":"2015","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22823","DOI":"10.1074\/jbc.M701758200","article-title":"Differentially spliced isoforms of FAT1 are asymmetrically distributed within migrating cells","volume":"282","author":"Braun","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1038\/onc.2012.393","article-title":"FAT1 acts as an upstream regulator of oncogenic and inflammatory pathways, via PDCD4, in glioma cells","volume":"32","author":"Dikshit","year":"2013","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"98887","DOI":"10.18632\/oncotarget.21946","article-title":"Verteporfin inhibits gastric cancer cell growth by suppressing adhesion molecule FAT1","volume":"8","author":"Kang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/cas.15394","article-title":"Oncogenic LINC00857 recruits TFAP2C to elevate FAT1 expression in gastric cancer","volume":"114","author":"Zhang","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3892\/ijmm.2020.4665","article-title":"Sulforaphane suppresses the viability and metastasis, and promotes the apoptosis of bladder cancer cells by inhibiting the expression of FAT-1","volume":"46","author":"Wang","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1007\/s10528-021-10148-6","article-title":"Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression","volume":"60","author":"Ma","year":"2022","journal-title":"Biochem. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1459368","DOI":"10.1155\/2020\/1459368","article-title":"circFAT1(e2) Promotes Papillary Thyroid Cancer Proliferation, Migration, and Invasion via the miRNA-873\/ZEB1 Axis","volume":"2020","author":"Liu","year":"2020","journal-title":"Comput. Math. Methods Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12943-018-0917-7","article-title":"CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells","volume":"17","author":"Liu","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_36","first-page":"2136","article-title":"FAT1 inhibits cell migration and invasion by affecting cellular mechanical properties in esophageal squamous cell carcinoma","volume":"39","author":"Hu","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"609","DOI":"10.21147\/j.issn.1000-9604.2019.04.05","article-title":"FAT1, a direct transcriptional target of E2F1, suppresses cell proliferation, migration and invasion in esophageal squamous cell carcinoma","volume":"31","author":"Wang","year":"2019","journal-title":"Chin. J. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8508","DOI":"10.1245\/s10434-021-10089-9","article-title":"Significance of Circular FAT1 as a Prognostic Factor and Tumor Suppressor for Esophageal Squamous Cell Carcinoma","volume":"28","author":"Takaki","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153569","DOI":"10.1016\/j.prp.2021.153569","article-title":"Linc8087 predicts favorable prognosis and inhibits cell migration and invasion in NSCLC","volume":"225","author":"Qi","year":"2021","journal-title":"Pathol. Res. Pract."},{"key":"ref_40","first-page":"1320","article-title":"FAT1 somatic mutations in head and neck carcinoma are associated with tumor progression and survival","volume":"39","author":"Lin","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41598-020-79524-3","article-title":"Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells","volume":"11","author":"Meng","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hsu, T.N., Huang, C.M., Huang, C.S., Huang, M.S., Yeh, C.T., Chao, T.Y., and Bamodu, O.A. (2019). Targeting FAT1 Inhibits Carcinogenesis, Induces Oxidative Stress and Enhances Cisplatin Sensitivity through Deregulation of LRP5\/WNT2\/GSS Signaling Axis in Oral Squamous Cell Carcinoma. Cancers, 11.","DOI":"10.3390\/cancers11121883"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/carcin\/bgu054","article-title":"Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma","volume":"35","author":"Valletta","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"870055","DOI":"10.3389\/fonc.2022.870055","article-title":"FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair","volume":"12","author":"Lan","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_45","first-page":"587","article-title":"Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of \u03b2-catenin","volume":"26","author":"Nishikawa","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2147\/JHC.S398573","article-title":"Comprehensive Genomic Profiling Identifies FAT1 as a Negative Regulator of EMT, CTCs, and Metastasis of Hepatocellular Carcinoma","volume":"10","author":"Huang","year":"2023","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.canlet.2016.09.014","article-title":"Integrative genomic and functional analysis of human oral squamous cell carcinoma cell lines reveals synergistic effects of FAT1 and CASP8 inactivation","volume":"383","author":"Hayes","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1074\/jbc.M809333200","article-title":"Atrophin proteins interact with the Fat1 cadherin and regulate migration and orientation in vascular smooth muscle cells","volume":"284","author":"Hou","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e009","DOI":"10.1621\/nrs.06009","article-title":"Atrophin proteins: An overview of a new class of nuclear receptor corepressors","volume":"6","author":"Wang","year":"2008","journal-title":"Nucl. Recept. Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.yjmcc.2013.10.013","article-title":"Angiotensin II induces Fat1 expression\/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation","volume":"66","author":"Chinnasamy","year":"2014","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1128\/MCB.23.10.3575-3582.2003","article-title":"Mice lacking the giant protocadherin mFAT1 exhibit renal slit junction abnormalities and a partially penetrant cyclopia and anophthalmia phenotype","volume":"23","author":"Ciani","year":"2003","journal-title":"Mol. Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/12\/1621\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:54:27Z","timestamp":1760126067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/12\/1621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,14]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cells12121621"],"URL":"https:\/\/doi.org\/10.3390\/cells12121621","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,14]]}}}