Journal
CANCER CELL
Volume 22, Issue 5, Pages 571-584Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2012.08.013
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Funding
- Instituto de Salud Carlos III FEDER [RD09/0076/00036]
- Xarxa de Bancs de tumors
- Pla Director d'Oncologia de Catalunya (XBTC)
- European Research Council [208488]
- Consolider programmes (MICINN)
- Spanish Ministry of Science and Innovation [SAF2006-02170, SAF2009-11757]
- National Institutes of Health [CA34610]
- Fundacion BBVA
- MICINN [Grants PS09/00965]
- NanoCoMets (CIBERBBN)
- European Research Council (ERC) [208488] Funding Source: European Research Council (ERC)
- ICREA Funding Source: Custom
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A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-beta pathway, yet, paradoxically, they are characterized by elevated TGF-beta production. Here, we unveil a prometastatic program induced by TGF-beta in the microenvironment that associates with a high risk of CRC relapse upon treatment. The activity of TGF-beta 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-beta-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-beta stromal program for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC.
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