Glucose and Palmitic Acid Induce Colon Cancer Cell Centrosome Amplification through ROCK1-KIF2A Pathway
WANG Pu1*, DU Bin2, NIU Zixu3, ZHOU Feilun3, LI Shaoqin4
This work was to investigate how microtubule depolymerase KIF2A was involved in centrosome amplification induced by glucose and palmitic acid in colon cancer HCT116 cells. HCT116 cells were co-treated with glucose (25 mmol/L) and palmitic acid (150 μmol/L), and then immunoprecipitated with ROCK1 antibody, and the precipitation results were identified by high throughput mass spectrometry HPLC/MS. Western blot, siRNA and immunofluorescence were used to verify the interacting proteins of ROCK1. The results showed that the centrosomal located ROCK1 could bind to the centrosomal protein-located microtubule depolymerase KIF2A after treatment with glucose and palmitic acid. Knockdown of KIF2A expression could reduce the amplification rate of centrosomes induced by glucose and palmitic acid. Bioinformatics analysis showed that the mRNA expression level of KIF2A in cancer tissue was significantly higher than that in healthy tissue (healthy tissues 3.275±0.385, Stage I 4.460±0.6818, Stage II 4.436±0.620, Stage III 4.365±0.680, Stage IV 4.442±0.555, P<0.01), there is no difference in the expression of KIF2A in colon cancer tissues of different clinical stages. The low KIF2A expression was positively correlated with poor prognosis of colon cancer (median survival: low expression 1 765 days vs high expression 3 042 days, P<0.01). In conclusion, ROCK1-KIF2A pathway plays a key role in centrosome amplification induced by glucose and palmitic acid, which provides experimental basis for comprehensive prevention and treatment of diabetes-related colon cancer.
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