Cancer Cell 2012,
PMID: 23153532
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; Batlle, Eduard
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.
Diseases/Pathways annotated by Medline MESH: Colorectal Neoplasms, Neoplasm Metastasis, Recurrence
Document information provided by NCBI PubMed
Text Mining Data
GP130/STAT3 → IL11: "
Secretion of
IL11 by TGF-ß stimulated cancer associated fibroblasts ( CAFs )
triggers GP130/STAT3 signaling in tumor cells
"
GP130/STAT3 → IL11: "
Secretion of IL11 by TGF-ß stimulated cancer associated fibroblasts ( CAFs ) triggers GP130/STAT3 signaling in tumor cells
"
Manually curated Databases
No curated data.