Study On The Role And Mechanism Of AGK In The Occurrence And Development Of Colorectal Cancer

Acylglycerol kinase(AGK)is a lipid kinase that catalyzes the formation of phosphatidic acid and lysophosphatidic acid,participates in the synthesis of phospholipids or acts as a cell signaling molecule,and can regulate various malignant processes,such as tumor cell proliferation,migration,invasion and angiogenesis.However,there are few studies on the role and mechanism of AGK in colorectal cancer,and there were no published studies on the role of AGK in the phenotype of CRC.In this study,the pathological specimens of colorectal cancer patients,colorectal cancer cell lines,and nude mice were used as research objects,and we found that AGK can inhibit cell proliferation and promote cell senescence of colorectal cancer.The expression of AGK in colorectal cancer specimens is significantly lower than that in adjacent normal mucosal tissues.The cell proliferation level of the AGK stable low-expressed cell lines was significantly higher than that of the control cells,while the cell senescence level was significantly lower than that of the control group.Further mechanism study found that AGK can not only bind p53 and phosphorylate it,thus inhibiting mdm2-mediated ubiquitination degradation of p53,but also inhibit the lysosomal degradation pathway of p53 through the PINK1/Parkin signaling pathway,thereby promoting transcriptional activation of p21,and then affecting cell proliferation and cellular senescence.This study revealed the important role of the AGK / p53 / p21 axis in colorectal cancer,and provided a new perspective and method for tumor prevention and treatment strategies.