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Cell Press, Cancer Cell, 5(22), p. 571-584, 2012

DOI: 10.1016/j.ccr.2012.08.013

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Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation

Journal article published in 2012 by Alexandre Calon, Sergio Palomo-Ponce, Daniele V. F. Tauriello, Mar Iglesias, Xiang H.-F. Zhang ORCID, Marta Sevillano, Cristina Nadal, Elisa Espinet ORCID, Peter Jung, María Virtudes Céspedes, Antoni Riera ORCID, David Rossell, Ramón Mangues, Daniel Byrom, Joan Massagué and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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 programme 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 signalling in tumour cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-beta stromal programme for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC.