The Molecular Mechanism Of CPT1A Promoting The Invasion And Migration Of Esophageal Cancer Cells

Esophageal Cancer has rapid progress and poor prognosis,and its mortality rate ranks fourth in China.Despite we had significant advances in technology of surgery and adjuvant chemotherapy,the five-year survival rate remains low in patients with esophageal cancer.Therefore,it has a great significane to improve the diagnosis and treatment of esophageal caner by identifying key molecules of esophageal cancer and exploring the possible molecular markers and potential targets.Our previous study found that gain of CPT1A was negatively correlated with overall survival.The result of immunohistochemistry showed that overexpression of CPT1A was significantly associated with poor prognosis in patients with esophageal squmous cell carinoma,and was an independent prognostic factor.In vitro,knockdown of CPT1A significantly inhibited the invasion and migration of KYSE510 and KYSE450 cells.Based on the results of gene expression profiles,we will screen out the targeted gene related to migration and invasion of tumor cells.In this study,we found that knockdown of CPT1A could down-regulate the mRNA and protein levels of uPA by RT-PCR and western blotting.We further found that knockdown of CPT1A inhibited the phosphorylation of NF-кB p65,and knockdown of NF-кB p65 mimiced the effects of CPT1A on the invasion and migration of ESCC cells and uPA protein and mRNA levels.PKCiota and p62 are reported as the upstream regulators of the NF-кB signaling pathway.In our study,we revealed that knockdown of CPT1A could down-regulate the protein expressions of PKCiota and p62.And,there is a feedback effect between PKCiota and p62.In KYSE450 cells.knockdown of PKCiota can reduce the expressions of uPA and p62 and inhibit phosphorylation of p65.After knockdown of CPT1A or PKCiota,we treated KYSE450 cells with MG 132,and the results showed that MG 132 could rescue the expression of p62 which was decreased by CPT1A or PKCiota siRNAs.Interestingly,knockdown of NF-кB p65 also decreased the protein expression of CPT1A.In summary,knockdown of CPT1A inhibits the invasion and migration of ESCC cells via inhibting PKCiota/p62/NF-кB/uPA axis.In this paper,we explain the molecular mechanism of CPT1A promoting the migration and invasion of ESCC cells,which is expected to be a new molecular target for the treatment of ESCC.