SKA1 Regulates the Invasion and Metastasis of Pancreatic Cancer Cells via Cdc42 Mediated Golgi Stacking
Objective:To explore the molecular mechanism of SKA1 regulating invasion and metastasis of pancreatic ductal ade-nocarcinoma(PDAC).Methods:Immunohistochemical staining was used to detect the expression levels of SKA1 and Cdc42 in pancreatic cancer tissue samples and paired para-cancer tissues,and western blot was used to verify the expression levels of SKA1 and Cdc42 in dif-ferent pancreatic cancer cell lines and normal pancreatic ductal epithelial cells.Pancreatic cancer cell lines with SKA1 stable knockdown and overexpression were constructed by lentivirus transfection technique.The effect of SKA1 knockdown or overexpression on Golgi structure in PDAC cells and the regulation of Cdc42 inhibitor ZCL278 on Golgi structure were detected by immunofluorescence method.The effect of ZCL278 on cancer metastasis induced by SKA1 overexpression was detected by Transwell assay and cell scratch formation assay.The effects of SKA1 and Cdc42 expression on autophagy markers were detected by western blotting.Results:The expressions of SKA1 and Cdc42 in pancreatic ductal adenocarcinoma tissues and cells were significantly higher than those in normal tissues or cells,and the expressions of SKA1 and CDC42 were significantly positively correlated.Patients with low SKA1 expression were found to have a longer overall survival time,while high or low Cdc42 expression was not associated with overall survival.We then found that SKA1 promotes Golgi stacking in PDAC cells and that the Cdc42 inhibitor ZCL278 inhibits this stacking phenomenon in SKA1 overexpressed PDAC cells.Further,we found that inhibition of Cdc42 could reverse the promoting effect of SKA1 overexpression on pancreatic cancer invasion and metastasis,with statistical difference,while there was no significant difference in cells with non-high SKA1 expression.Fi-nally,we found that Cdc42 could induce autophagy of PDAC cells by the regulation of SKA 1.Conclusions:SKA1 influences autophagy of PDAC by regulating the dense Golgi stacking mediated by Cdc42,and finally promotes the migration and invasion of pancreatic can-cer cells.
Pancreatic ductal adenocarcinomaSpindle and kinetochore-associated protein 1Golgi apparatusCell division cycle 42
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