The binding between ROCK1 and KIF2A signals for the centrosome amplification triggered by high glucose, insulin and palmitic acid

Background: Diabetes increases the risk for various cancers without established mechanisms. Centrosome amplification can initiate tumorigenesis in genetically modified cells. However, the findings from genetically modified experimental models may be far away from reality. We have reported that diabetes promotes the occurrence of centrosome amplification in different types of cells, implicating that centrosome amplification is a candidate mechanism underlying the diabetes-promoted tumorigenesis. In the present study, we investigated the molecular mechanisms of the centrosome amplification triggered by high glucose, insulin and palmitic acid using HCT116 colon cancer cells as an experimental model. Results: : We found that KIF2A was localized in the centrosomes. The experimental treatment induced the binding between ROCK1 and KIF2A, although did not increase the protein level of KIF2A. The molecular docking modeling analysis also showed that the two proteins had the binding/interaction potential. We used siRNA of each protein to knockdown their expression level, as a tool to disrupt the ROCK1-KIF2A complex, which attenuated the treatment-induced centrosome amplification. Conclusions: : Our results suggest that the binding between ROCK1 and KIF2A signals for the diabetes-associated centrosome amplification. This provides a molecular target for the inhibition of the centrosome amplification, which might be required for assessing the role of centrosome amplification in cancer in the nature, such as cancer in diabetes.