Author/Authors :
Frédéric Calon، نويسنده , , Alexandre and Espinet، نويسنده , , Elisa and Palomo-Ponce، نويسنده , , Sergio and Tauriello، نويسنده , , Daniele V.F. and Iglesias، نويسنده , , Mar and Céspedes، نويسنده , , Marيa Virtudes and Sevillano، نويسنده , , Marta and Nadal، نويسنده , , Cristina and Jung، نويسنده , , Peter and Zhang، نويسنده , , Xiang H.-F. and Byrom، نويسنده , , Daniel and Riera، نويسنده , , Antoni and Rossell، نويسنده , , David and Mangues، نويسنده , , Ramَn and Massagué، نويسنده , , Joan and Sancho، نويسنده , , Elena and Batlle، نويسنده , , Eduard، نويسنده ,
Abstract :
Summary
e 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.
