TIF1γ Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability

The transcription accessory factor TIF1 gamma/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 TIF1 gamma inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1 gamma deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo. Clinically, reduced TIF1 gamma expression in human tumors correlated with an increased rate of genomic rearrangements. Overall, our work indicates that TIF1 gamma exerts its tumor-suppressive functions in part by promoting chromosomal stability. (C) 2015 AACR.