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http://hdl.handle.net/2445/208724
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DC Field | Value | Language |
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dc.contributor.author | Sanchez Tillo, E. | - |
dc.contributor.author | Pedrosa, Leire | - |
dc.contributor.author | Vila, I. | - |
dc.contributor.author | Chen, Yao | - |
dc.contributor.author | Gyorffy, B. | - |
dc.contributor.author | Sánchez Moral, L. | - |
dc.contributor.author | Siles Mena, Laura | - |
dc.contributor.author | Lozano Salvatella, Juan José | - |
dc.contributor.author | Esteve Codina, A. | - |
dc.contributor.author | Darling, Douglas S. | - |
dc.contributor.author | Cuatrecasas Freixas, Miriam | - |
dc.contributor.author | Castells Garangou, Antoni | - |
dc.contributor.author | Maurel Santasusana, Joan | - |
dc.contributor.author | Postigo, Antonio | - |
dc.date.accessioned | 2024-03-13T12:14:34Z | - |
dc.date.available | 2024-03-13T12:14:34Z | - |
dc.date.issued | 2023-10-23 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.uri | http://hdl.handle.net/2445/208724 | - |
dc.description.abstract | 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 cells and negatively in BRAF-mutant CRC cells with gene signatures for EMT, cell proliferation and survival, and ERK signaling. On a mechanistic level, ZEB1 knockdown in KRAS-mutant CRC cells increased apoptosis and reduced clonogenicity and anchorage-independent growth; the reverse occurred in BRAFV600E CRC cells. ZEB1 is associated with better prognosis and reduced EMT signature in patients harboring BRAF CRCs. These data suggest that ZEB1 can function as a tumor suppressor in BRAF-mutant CRCs, highlighting the importance of considering the KRAS/BRAF mutational background of CRCs in therapeutic strategies targeting ZEB1/EMT. | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Clinical Investigation | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1172/jci.insight.164629 | - |
dc.relation.ispartof | Jci Insight, 2023, vol. 8, num. 20, p. e164629 | - |
dc.relation.uri | https://doi.org/10.1172/jci.insight.164629 | - |
dc.rights | cc by (c) Sánchez Tilló, Ester et al., 2023 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Transducció de senyal cel·lular | - |
dc.subject.other | Carcinoma | - |
dc.subject.other | Signal Transduction | - |
dc.title | The EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2024-03-05T13:32:07Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.idimarina | 9379866 | - |
dc.identifier.pmid | 37870961 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
Files in This Item:
File | Description | Size | Format | |
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JCI Insight.pdf | 21.36 MB | Adobe PDF | View/Open |
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