{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:14:44Z","timestamp":1793654084354,"version":"4.5.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"7842","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2021,1,21]]},"DOI":"10.1038\/s41586-020-03046-1","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T12:09:05Z","timestamp":1608120545000},"page":"448-455","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":399,"title":["Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis"],"prefix":"10.1038","volume":"589","author":[{"given":"Ievgenia","family":"Pastushenko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Mauri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-9172","authenticated-orcid":false,"given":"Yura","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"de Cock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"Meeusen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-9342","authenticated-orcid":false,"given":"Benjamin","family":"Swedlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-9616","authenticated-orcid":false,"given":"Francis","family":"Impens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-5631","authenticated-orcid":false,"given":"Delphi","family":"Van Haver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Opitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9968-1779","authenticated-orcid":false,"given":"Manuel","family":"Thery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacine","family":"Bareche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Lapouge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Vermeersch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-1784","authenticated-orcid":false,"given":"Yves-R\u00e9mi","family":"Van Eycke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Balsat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Decaestecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youri","family":"Sokolow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Hassid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Perez-Bustillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Agreda-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Rios-Buceta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Jaen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Redondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-5679","authenticated-orcid":false,"given":"Ramon","family":"Sieira-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2481-7800","authenticated-orcid":false,"given":"Jose F.","family":"Millan-Cayetano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onofre","family":"Sanmatrtin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicky","family":"D\u2019Haene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Moers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Rozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Blondeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lemaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Scozzaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6772-8448","authenticated-orcid":false,"given":"Veerle","family":"Janssens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"De Troya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"P\u00e9rez-Morga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Salmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-9977","authenticated-orcid":false,"given":"Christos","family":"Sotiriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6822-1246","authenticated-orcid":false,"given":"Francoise","family":"Helmbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-4322","authenticated-orcid":false,"given":"C\u00e9dric","family":"Blanpain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"3046_CR1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/ng.2538","volume":"45","author":"LG Morris","year":"2013","unstructured":"Morris, L. G. et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat. Genet. 45, 253\u2013261 (2013).","journal-title":"Nat. Genet."},{"key":"3046_CR2","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.ccell.2016.04.004","volume":"29","author":"GP Dotto","year":"2016","unstructured":"Dotto, G. P. & Rustgi, A. K. Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell 29, 622\u2013637 (2016).","journal-title":"Cancer Cell"},{"key":"3046_CR3","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41568-018-0024-5","volume":"18","author":"A S\u00e1nchez-Dan\u00e9s","year":"2018","unstructured":"S\u00e1nchez-Dan\u00e9s, A. & Blanpain, C. Deciphering the cells of origin of squamous cell carcinomas. Nat. Rev. Cancer 18, 549\u2013561 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"3046_CR4","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","volume":"578","author":"The ICGC\/TCGA Pan-Cancer Analysis of Whole Genomes Consortium","year":"2020","unstructured":"The ICGC\/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature 578, 82\u201393 (2020).","journal-title":"Nature"},{"key":"3046_CR5","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nature12912","volume":"505","author":"MS Lawrence","year":"2014","unstructured":"Lawrence, M. S. et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505, 495\u2013501 (2014).","journal-title":"Nature"},{"key":"3046_CR6","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.ccell.2018.11.006","volume":"34","author":"Z Li","year":"2018","unstructured":"Li, Z. et al. Loss of the FAT1 tumor suppressor promotes resistance to CDK4\/6 inhibitors via the Hippo pathway. Cancer Cell 34, 893\u2013905.e8 (2018).","journal-title":"Cancer Cell"},{"key":"3046_CR7","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nm.3878","volume":"21","author":"D Nassar","year":"2015","unstructured":"Nassar, D., Latil, M., Boeckx, B., Lambrechts, D. & Blanpain, C. Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma. Nat. Med. 21, 946\u2013954 (2015).","journal-title":"Nat. Med."},{"key":"3046_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04590-1","volume":"9","author":"D Martin","year":"2018","unstructured":"Martin, D. et al. Assembly and activation of the Hippo signalome by FAT1 tumor suppressor. Nat. Commun. 9, 2372 (2018).","journal-title":"Nat. Commun."},{"key":"3046_CR9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.canlet.2017.03.033","volume":"397","author":"X Hu","year":"2017","unstructured":"Hu, X. et al. FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK\/ERK signaling pathway in esophageal squamous cell cancer. Cancer Lett. 397, 83\u201393 (2017).","journal-title":"Cancer Lett."},{"key":"3046_CR10","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1002\/ijc.31092","volume":"142","author":"C Srivastava","year":"2018","unstructured":"Srivastava, C. et al. FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma. Int. J. Cancer 142, 805\u2013812 (2018).","journal-title":"Int. J. Cancer"},{"key":"3046_CR11","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-018-0040-3","volume":"556","author":"I Pastushenko","year":"2018","unstructured":"Pastushenko, I. et al. Identification of the tumour transition states occurring during EMT. Nature 556, 463\u2013468 (2018).","journal-title":"Nature"},{"key":"3046_CR12","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.stem.2016.10.018","volume":"20","author":"M Latil","year":"2017","unstructured":"Latil, M. et al. Cell-type-specific chromatin states differentially prime squamous cell carcinoma tumor-initiating cells for epithelial to mesenchymal transition. Cell Stem Cell 20, 191\u2013204.e5 (2017).","journal-title":"Cell Stem Cell"},{"key":"3046_CR13","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.tcb.2018.12.001","volume":"29","author":"I Pastushenko","year":"2019","unstructured":"Pastushenko, I. & Blanpain, C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29, 212\u2013226 (2019).","journal-title":"Trends Cell Biol."},{"key":"3046_CR14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","volume":"166","author":"MA Nieto","year":"2016","unstructured":"Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016. Cell 166, 21\u201345 (2016).","journal-title":"Cell"},{"key":"3046_CR15","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nature13305","volume":"511","author":"S Boumahdi","year":"2014","unstructured":"Boumahdi, S. et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature 511, 246\u2013250 (2014).","journal-title":"Nature"},{"key":"3046_CR16","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.ccell.2016.09.001","volume":"30","author":"G Ferone","year":"2016","unstructured":"Ferone, G. et al. SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin. Cancer Cell 30, 519\u2013532 (2016).","journal-title":"Cancer Cell"},{"key":"3046_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5511","volume":"5","author":"JM Siegle","year":"2014","unstructured":"Siegle, J. M. et al. SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma. Nat. Commun. 5, 4511 (2014).","journal-title":"Nat. Commun."},{"key":"3046_CR18","doi-asserted-by":"publisher","first-page":"44962","DOI":"10.1074\/jbc.M209427200","volume":"277","author":"CD Cooper","year":"2002","unstructured":"Cooper, C. D. & Lampe, P. D. Casein kinase 1 regulates connexin-43 gap junction assembly. J. Biol. Chem. 277, 44962\u201344968 (2002).","journal-title":"J. Biol. Chem."},{"key":"3046_CR19","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1042\/bj3570843","volume":"357","author":"CA Lewis","year":"2001","unstructured":"Lewis, C. A., Townsend, P. A. & Isacke, C. M. Ca2+\/calmodulin-dependent protein kinase mediates the phosphorylation of CD44 required for cell migration on hyaluronan. Biochem. J. 357, 843\u2013850 (2001).","journal-title":"Biochem. J."},{"key":"3046_CR20","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1021\/pr1008702","volume":"10","author":"RY Huang","year":"2011","unstructured":"Huang, R. Y. et al. Identification of CaMKII phosphorylation sites in connexin43 by high-resolution mass spectrometry. J. Proteome Res. 10, 1098\u20131109 (2011).","journal-title":"J. Proteome Res."},{"key":"3046_CR21","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13045-018-0605-5","volume":"11","author":"C Chen","year":"2018","unstructured":"Chen, C., Zhao, S., Karnad, A. & Freeman, J. W. The biology and role of CD44 in cancer progression: therapeutic implications. J. Hematol. Oncol. 11, 64 (2018).","journal-title":"J. Hematol. Oncol."},{"key":"3046_CR22","doi-asserted-by":"publisher","first-page":"031908","DOI":"10.1063\/1.5024874","volume":"2","author":"MK Jolly","year":"2018","unstructured":"Jolly, M. K. et al. Interconnected feedback loops among ESRP1, HAS2, and CD44 regulate epithelial\u2013mesenchymal plasticity in cancer. APL Bioeng. 2, 031908 (2018).","journal-title":"APL Bioeng."},{"key":"3046_CR23","doi-asserted-by":"publisher","first-page":"29086","DOI":"10.1074\/jbc.M211074200","volume":"278","author":"MA Chellaiah","year":"2003","unstructured":"Chellaiah, M. A., Biswas, R. S., Rittling, S. R., Denhardt, D. T. & Hruska, K. A. Rho-dependent Rho kinase activation increases CD44 surface expression and bone resorption in osteoclasts. J. Biol. Chem. 278, 29086\u201329097 (2003).","journal-title":"J. Biol. Chem."},{"key":"3046_CR24","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nm.4247","volume":"23","author":"S G\u00f6llner","year":"2017","unstructured":"G\u00f6llner, S. et al. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia. Nat. Med. 23, 69\u201378 (2017).","journal-title":"Nat. Med."},{"key":"3046_CR25","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nrm.2016.76","volume":"17","author":"A Avgustinova","year":"2016","unstructured":"Avgustinova, A. & Benitah, S. A. Epigenetic control of adult stem cell function. Nat. Rev. Mol. Cell Biol. 17, 643\u2013658 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"3046_CR26","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nrm.2017.87","volume":"18","author":"T Panciera","year":"2017","unstructured":"Panciera, T., Azzolin, L., Cordenonsi, M. & Piccolo, S. Mechanobiology of YAP and TAZ in physiology and disease. Nat. Rev. Mol. Cell Biol. 18, 758\u2013770 (2017).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"3046_CR27","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/S1470-2045(15)70124-5","volume":"16","author":"JP Machiels","year":"2015","unstructured":"Machiels, J. P. et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 16, 583\u2013594 (2015).","journal-title":"Lancet Oncol."},{"key":"3046_CR28","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1016\/S1470-2045(17)30679-4","volume":"18","author":"D Planchard","year":"2017","unstructured":"Planchard, D. et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 18, 1307\u20131316 (2017).","journal-title":"Lancet Oncol."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03046-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03046-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-03046-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T18:01:44Z","timestamp":1684605704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-020-03046-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,16]]},"references-count":28,"journal-issue":{"issue":"7842","published-print":{"date-parts":[[2021,1,21]]}},"alternative-id":["3046"],"URL":"https:\/\/doi.org\/10.1038\/s41586-020-03046-1","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739227643.793583119","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,16]]},"assertion":[{"value":"21 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.\u00a0Blanpain, I.P. and F.M. are co-inventors on a patent application on the use of SRC inhibitors for the treatment of <i>FAT1<\/i>-mutated cancers.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}