Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

Calon, Alexandre; Lonardo, Enza; Berenguer-Llergo, Antonio; Espinet, Elisa; Hernando-Momblona, Xavier; Iglesias Coma, Mar; Sevillano, Marta; Palomo-Ponce, Sergio; Tauriello, Daniele V.F.; Byrom, Daniel; Cortina Duran, Carme; Morral Martínez, Clara, 1989-; Barceló, Carles; Tosi, Sebastien; Riera, Antoni; Attolini, Camille Stephan-Otto; Rossell, David; Sancho, Elena; Batlle Gómez, Eduard

Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

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dc.contributor.author Calon, Alexandreca
dc.contributor.author Lonardo, Enzaca
dc.contributor.author Berenguer-Llergo, Antonioca
dc.contributor.author Espinet, Elisaca
dc.contributor.author Hernando-Momblona, Xavierca
dc.contributor.author Iglesias Coma, Marca
dc.contributor.author Sevillano, Martaca
dc.contributor.author Palomo-Ponce, Sergioca
dc.contributor.author Tauriello, Daniele V.F.ca
dc.contributor.author Byrom, Danielca
dc.contributor.author Cortina Duran, Carmeca
dc.contributor.author Morral Martínez, Clara, 1989-ca
dc.contributor.author Barceló, Carlesca
dc.contributor.author Tosi, Sebastienca
dc.contributor.author Riera, Antonica
dc.contributor.author Attolini, Camille Stephan-Ottoca
dc.contributor.author Rossell, Davidca
dc.contributor.author Sancho, Elenaca
dc.contributor.author Batlle Gómez, Eduardca
dc.date.accessioned 2015-04-08T10:54:25Z
dc.date.available 2015-04-08T10:54:25Z
dc.date.issued 2015
dc.description.abstract Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-β signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-β in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progressionca
dc.format.mimetype application/pdfca
dc.identifier.citation Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M. et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015 Apr;47(4):320-9. doi: 10.1038/ng.3225.ca
dc.identifier.doi http://dx.doi.org/10.1038/ng.3225
dc.identifier.issn 1061-4036
dc.identifier.uri http://hdl.handle.net/10230/23362
dc.language.iso engca
dc.publisher Nature Publishing Group
dc.relation.ispartof Nature Genetics. 2015 Apr;47(4):320-9
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Còlon -- Càncerca
dc.title Stromal gene expression defines poor-prognosis subtypes in colorectal cancerca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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