FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer
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- dc.contributor.author Peláez García, Albertoca
- dc.contributor.author Barderas, Rodrigoca
- dc.contributor.author Torres, Sofíaca
- dc.contributor.author Teixidó, Joaquínca
- dc.contributor.author Bonilla, Félixca
- dc.contributor.author García de Herreros, Antonioca
- dc.contributor.author Hernández-Varas, Pabloca
- dc.contributor.author Casal, José Ignacioca
- dc.date.accessioned 2015-05-13T10:41:59Z
- dc.date.available 2015-05-13T10:41:59Z
- dc.date.issued 2013ca
- dc.description.abstract Fibroblast growth factor receptor 4 (FGFR4) is vital in early development and tissue repair. FGFR4 expression levels are very restricted in adult tissues, except in several solid tumors including colorectal cancer, which showed overexpression of FGFR4. Here, FGFR4 mutation analysis discarded the presence of activating mutations, other than Arg388, in different colorectal cancer cell lines and tumoral samples. Stable shRNA FGFR4-silencing in SW480 and SW48 cell lines resulted in a significant decrease in cell proliferation, adhesion, cell migration and invasion. This decrease in the tumorigenic and invasive capabilities of colorectal cancer cells was accompanied by a decrease of Snail, Twist and TGFβ gene expression levels and an increase of E-cadherin, causing a reversion to a more epithelial phenotype, in three different cell lines. In addition, FGFR4-signaling activated the oncogenic SRC, ERK1/2 and AKT pathways in colon cancer cells and promoted an increase in cell survival. The relevance of FGFR4 in tumor growth was supported by two different strategies. Kinase inhibitors abrogated FGFR4-related cell growth and signaling pathways at the same extent than FGFR4-silenced cells. Specific FGFR4-targeting using antibodies provoked a similar reduction in cell growth. Moreover, FGFR4 knock-down cells displayed a reduced capacity for in vivo tumor formation and angiogenesis in nude mice. Collectively, our data support a crucial role for FGFR4 in tumorigenesis, invasion and survival in colorectal cancer. In addition, FGFR4 targeting demonstrated its applicability for colorectal cancer therapy.en
- dc.description.sponsorship This research was supported by grant BIO2009-08818 from the Spanish Ministry of Science and Innovation, grant to established research groups (AECC) and grant S2011/BMD-2344/Colomics2 from Comunidad de Madrid.en
- dc.format.mimetype application/pdfca
- dc.identifier.citation Peláez-García A, Barderas R, Torres S, Hernández-Varas P, Teixidó J, Bonilla F et al. FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal cancer. PLoS ONE. 2013;8(5):e63695. DOI: 10.1371/journal.pone.0063695ca
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0063695
- dc.identifier.issn 1932-6203ca
- dc.identifier.uri http://hdl.handle.net/10230/23571
- dc.language.iso engca
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS ONE. 2013;8(5):e63695
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2009-08818
- dc.rights © 2013 Peláez-García et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Cèl·lules -- Proliferació
- dc.subject.other Apoptosica
- dc.title FGFR4 role in epithelial-mesenchymal transition and its therapeutic value in colorectal canceren
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca