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TIF1gamma Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability.

Roxane M Pommier, Johann Gout, David F Vincent, Lindsay B Alcaraz, Nicolas Chuvin, Vanessa Arfi, Sylvie Martel, Bastien Kaniewski, Guillaume Devailly, Genevieve Fourel, Pascal Bernard, Caroline Moyret-Lalle, Stephane Ansieau, Alain Puisieux, Ulrich Valcourt, Stephanie Sentis, and Laurent Bartholin (2015)

Cancer Res, 75(20):4335-50.

The transcription accessory factor TIF1gamma/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 TIF1gamma inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1gamma deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo. Clinically, reduced TIF1gamma expression in human tumors correlated with an increased rate of genomic rearrangements. Overall, ourwork indicates that TIF1gamma exerts its tumor-suppressive functions in part by promoting chromosomal stability.

 
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