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Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation
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Calon, Alexandre, Espinet, Elisa, Palomo-Ponce, Sergio, Tauriello, Daniele V.F., Iglesias, Mar, Céspedes, María Virtudes, Sevillano, Marta, Nadal, Cristina, Jung, Peter, Zhang, Xiang H.-F., Byrom, Daniel, Riera, Antoni, Rossell, David, Mangues, Ramón, Massagué, Joan, Sancho, Elena and Batlle, Eduard (2012) Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell, Volume 22 (Number 5). pp. 571-584. doi:10.1016/j.ccr.2012.08.013 ISSN 1535-6108.
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Official URL: http://dx.doi.org/10.1016/j.ccr.2012.08.013
Abstract
A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-β pathway, yet, paradoxically, they are characterized by elevated TGF-β production. Here, we unveil a prometastatic program induced by TGF-β in the microenvironment that associates with a high risk of CRC relapse upon treatment. The activity of TGF-β on stromal cells increases the efficiency of organ colonization by CRC cells, whereas mice treated with a pharmacological inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by TGF-β-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3 signaling in tumor cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-β stromal program for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics | ||||
Journal or Publication Title: | Cancer Cell | ||||
Publisher: | Cell Press | ||||
ISSN: | 1535-6108 | ||||
Official Date: | 13 November 2012 | ||||
Dates: |
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Volume: | Volume 22 | ||||
Number: | Number 5 | ||||
Page Range: | pp. 571-584 | ||||
DOI: | 10.1016/j.ccr.2012.08.013 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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