ALEXANDRE CALON

A TGF-BETA DRIVEN PROGRAM IN STROMAL CELLS MEDIATES PROGRESSION TO METASTASIS

Alexandre CALON
(IRB Barcelon)

 Summary : Recent molecular classifications of CRC have defined subtypes displaying resistance to therapy and poor prognosis. We have re-evaluated the classifications under our perspective and discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. We discovered that high activity of TGF-beta on stromal cells increases the efficiency of organ colonization by CRC cells whereas low stromal TGF-beta signaling is a robust predictor of patient disease-free survival. We realized that especially fibroblasts activated in cancer (CAFs) had the capacity to increase the frequency of tumor-initiating cells, an effect dramatically enhanced by TGF-beta. Finally, we demonstrated the therapeutic potential of TGF-beta inhibition to prevent colorectal cancer progression to metastasis.

Recent publications :

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, Cortina C, Morral C, Barceló C, Tosi S, Riera A, Attolini CS, Rossell D, Sancho E, Batlle E. : Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015 Apr;47(4):320-9.
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, Sevillano M, Nadal C, Jung P, Zhang XH, Byrom D, Riera A, Rossell D, Mangues R, Massagué J, Sancho E, Batlle E. : Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012 Nov 13;22(5):571-84.