TIF1γ Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-10, Vol.75 (20), p.4335-4350
• Main Authors: Pommier, Roxane M, Gout, Johann, Vincent, David F, Alcaraz, Lindsay B, Chuvin, Nicolas, Arfi, Vanessa, Martel, Sylvie, Kaniewski, Bastien, Devailly, Guillaume, Fourel, Geneviève, Bernard, Pascal, Moyret-Lalle, Caroline, Ansieau, Stéphane, Puisieux, Alain, Valcourt, Ulrich, Sentis, Stéphanie, Bartholin, Laurent
• Format: Article
• Language: English
• Subjects: Animals; Carcinoma in Situ; Cell Cycle Checkpoints - genetics; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chromosomal Instability; Disease Models, Animal; Disease Progression; Down-Regulation; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Life Sciences; Mice; Mice, Knockout; Mitosis - genetics; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Ploidies; Spindle Apparatus - metabolism; Transcription Factors - metabolism
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-14-3426

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.