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Cancer Cell. 2012 Nov 13;22(5):571-84. doi: 10.1016/j.ccr.2012.08.013.

Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.

Author information

1
Oncology Programme, Institute for Research in Biomedicine, 08028 Barcelona, Spain.

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.

PMID:
23153532
PMCID:
PMC3512565
DOI:
10.1016/j.ccr.2012.08.013
[Indexed for MEDLINE]
Free PMC Article

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