biostudies-literatureSanchez-Tillo EAgència de Gestió d’Ajuts Universitaris i de RecercaSpanish Ministry of Science and InnovationOlga Torres FoundationSpanish Association Against CancerSpanish National Institute of Health Carlos IIIe164629https://www.ebi.ac.uk/biostudies/studies/S-EPMC10619495biostudies-literatureUnknown8(20)Despite being in the same pathway, mutations of KRAS and BRAF in colorectal carcinomas (CRCs) determine distinct progression courses. ZEB1 induces an epithelial-to-mesenchymal transition (EMT) and is associated with worse progression in most carcinomas. Using samples from patients with CRC, mouse models of KrasG12D and BrafV600E CRC, and a Zeb1-deficient mouse, we show that ZEB1 had opposite functions in KRAS- and BRAF-mutant CRCs. In KrasG12D CRCs, ZEB1 was correlated with a worse prognosis and a higher number of larger and undifferentiated (mesenchymal or EMT-like) tumors. Surprisingly, in BrafV600E CRC, ZEB1 was associated with better prognosis; fewer, smaller, and more differentiated (reduced EMT) primary tumors; and fewer metastases. ZEB1 was positively correlated in KRAS-mutant CRC cJCI insightThe EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas.PMC106194952017-SGR-11742021-SGR-01328AECC,PROYE19040POST_001PID2020-116338RB-I00CP13/00200,PI18/00244SAF2017-84918-RBiannual Grant A-2019/2020Siles LPedrosa LDarling DSLozano JJSanchez-Moral LVila IEsteve-Codina APostigo ACastells ASanchez-Tillo EMaurel JGyorffy BCuatrecasas MChen YfalseThe EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas.Despite being in the same pathway, mutations of KRAS and BRAF in colorectal carcinomas (CRCs) determine distinct progression courses. ZEB1 induces an epithelial-to-mesenchymal transition (EMT) and is associated with worse progression in most carcinomas. Using samples from patients with CRC, mouse models of KrasG12D and BrafV600E CRC, and a Zeb1-deficient mouse, we show that ZEB1 had opposite functions in KRAS- and BRAF-mutant CRCs. In KrasG12D CRCs, ZEB1 was correlated with a worse prognosis and a higher number of larger and undifferentiated (mesenchymal or EMT-like) tumors. Surprisingly, in BrafV600E CRC, ZEB1 was associated with better prognosis; fewer, smaller, and more differentiated (reduced EMT) primary tumors; and fewer metastases. ZEB1 was positively correlated in KRAS-mutant CRC c2023-01-01T00:00:00Z2023 Oct2026-05-29T12:18:55.737Z2025-04-20T01:34:12.337ZS-EPMC106194953787096110.1172/jci.insight.164629