C-Src Phosphorylates And Activates MAGL To Promote The Proliferation And Migration Of Pancreatic Cancer Cells

Pancreatic cancer,one of the most fatal malignant tumors,has shown dramatically increased incidence in recent years in China and is predicted to become the second leading cause of cancer death by 2030.Because the early clinical symptoms of pancreatic cancer are not obvious,diagnosis is difficult,combined with chemotherapy resistance and limited targeted therapy,the 5-year survival rate of pancreatic cancer patients is less than 5%.Therefore,in-depth study of the molecular mechanisms of pancreatic cancer occurrence and metastasis and finding effective targets for early diagnosis and treatment are of great significance for improving the survival rate of pancreatic cancer patients.The expansion of membrane structure is the basis of cell division,and a large amount of free fatty acids are needed for the synthesis of phospholipids and membranes before cell division.Monoacylglycerol lipase(MAGL)is highly expressed in pancreatic cancer cells.The free fatty acids produced by MAGL catalyzing the hydrolysis of monoacylglycerols(MAGs)are the main source of free fatty acids in invasive pancreatic cancer cells.However,whether its activity is regulated by posttranslational modification is still poorly understood.We found that c-Src can interact with MAGL and phosphorylate MAGL tyrosine 278 site.We have proved that the phosphorylation of MAGL Y278 significantly enhances its enzyme activity through in vitro protein and cell experiments.The enhancement of MAGL enzyme activity promotes the decomposition of lipid droplets in pancreatic cancer cells,thereby promoting the proliferation and migration of pancreatic cancer cells.The clinical database also shows that both c-Src and MAGL are highly expressed in pancreatic cancer tissues,and the high expression of c-Src or MAGL is closely related to the poor prognosis.The phosphorylation of c-Src and MAGL also showed a positive correlation in pancreatic cancer tissues.The above results indicate that c-Src enhances MAGL enzymatic activity by phosphorylating MAGL Y278,thereby promoting the proliferation and migration of pancreatic cancer cells.The research will not only expand people’s understanding of the carcinogenic mechanism of c-Src,but also provide evidence for MAGL as an anti-tumor target.