| Literature DB >> 23153532 |
Alexandre Calon1, Elisa Espinet, Sergio Palomo-Ponce, Daniele V F Tauriello, Mar Iglesias, María Virtudes Céspedes, Marta Sevillano, Cristina Nadal, Peter Jung, Xiang H-F Zhang, Daniel Byrom, Antoni Riera, David Rossell, Ramón Mangues, Joan Massagué, Elena Sancho, Eduard Batlle.
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.Entities:
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Year: 2012 PMID： 23153532 PMCID： PMC3512565 DOI： 10.1016/j.ccr.2012.08.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743