PCNA and JNK1-Stat3 pathways respectively promotes and inhibits diabetes-associated centrosome amplification by targeting at the ROCK1/14-3-3σ complex in human colon cancer HCT116 cells.

摘要: We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and translocation of rho-associated coiled-coil containing protein kinase 1 (ROCK1)/14-3-3σ complex in HCT116 cells. In functional proteomic study, we further investigated molecular pathways underlying using found treatment cells with high glucose, insulin, palmitic acid triggered increased expressions proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), 14-3-3σ. Individual knockdown PCNA, NPM, or 14-3-3σ inhibited amplification. Knockdown PCNA treatment-increased expression ROCK1, whereas ROCK1 did not affect expression. High also c-Jun N-terminal kinase-1 (JNK1) signal transducer activator transcription 3 (Stat3), individual which upregulated promoted contrast, overexpression JNK1 Stat3 enhanced Moreover, showed Stat3. JNK1, an effect on NPM vice versa. conclusion, our results suggest JNK1-Stat3 respectively feedback inhibits by targeting at ROCK1/14-3-3σ complex, serves as independent for