PCNA and JNK1-Stat3 pathways respectively promotes and inhibits centrosome amplification by targeting at the ROCK1/14-3-3σ complex
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ABSTRACT: We have recently reported that type 2 diabetes promotes cell centrosome amplification via enhancing the expression, biding and centrosome translocation of ROCK1/14-3-3σ complex. In the present functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using colon cancer HCT116 cells as experimental model. We found that treatment of cells with high glucose, insulin and palmitic acid triggered the centrosome amplification and increased the expressions of PCNA, NPM and 14-3-3σ. Individual knockdown of PCNA, NPM or 14-3-3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment-increased expression of ROCK1, while knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin and palmitic acid also increased the expressions of JNK1 and Stat3, individual knockdown of which up-regulated the treatment-increased expression of 14-3-3σ and promoted the centrosome amplification. In contrast, over-expression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14-3-3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment-increased expression of Stat3, but not the other way round. Knockdown of PCNA, JNK or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1-Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14-3-3σ complex, and NPM serves as an independent signal for the centrosome amplification.
ORGANISM(S): Homo Sapiens
SUBMITTER: Shao Chin Lee
PROVIDER: PXD009370 | iProX | Fri Mar 30 00:00:00 BST 2018
REPOSITORIES: iProX
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