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- TIF1γ Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability
TIF1γ Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability
Auteurs
Roxane M. Pommier, Johann Gout, David F. Vincent, Lindsay B. Alcaraz, Nicolas Chuvin, Vanessa Arfi, Sylvie Martel, Bastien Kaniewski, Guillaume Devailly, Geneviève Fourel, Pascal Bernard, Caroline Moyret-Lalle, Stéphane Ansieau, Alain Puisieux, Ulrich Valcourt, Stéphanie Sentis, Laurent Bartholin
Résumé
Abstract
The transcription accessory factor TIF1γ/TRIM33/RFG7/PTC7/Ectodermin functions as a tumor suppressor that promotes development and cellular differentiation. However, its precise function in cancer has been elusive. In the present study, we report that TIF1γ inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1γ deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo. Clinically, reduced TIF1γ expression in human tumors correlated with an increased rate of genomic rearrangements. Overall, our work indicates that TIF1γ exerts its tumor-suppressive functions in part by promoting chromosomal stability. Cancer Res; 75(20); 4335–50. ©2015 AACR.
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