Different Roles Of DEPTOR In Esophageal Cancer And Its Regulatory Mechanism

BackgroundIn today's world,esophageal cancer is ranked sixth in the cancer-causing cancer classification and eighth in the ranking of the incidence of malignancies,and therefore various studies on esophageal cancer are of paramount importance.DEPTOR plays a negative role in the mTOC1 and mTOC2 pathways.In normal tissues,DEPTOR inhibits the mTOR signaling pathway,whereas in many tumors,the expression of DEPTOR is decreased,leading to the activation of mTOR and tumor development.Therefore,most of DEPTOR is considered as a tumor suppressor,hindering tlhe tumor progression.However,in our literatures on DEPTOR and esophageal squamous cell carcinoma,we found that not all DEPTOR expression levels were reduced,and there were two diametrically opposite results for the patient's prognosis.Therefore,we boldly speculate that DEPTOR expression level in esophageal cancer and its role in tumor progression may have different results,and we start the experiniment on these bases.Methods1.To confirm the expression of DEPTOR in normal tissues and cancer tissues,we collected fresh clinical tissue samples and bought tissue chips for the survival analysis of esophageal cancer patients.2.The cell experiment was carried out in human normal immortalized esophageal epithelial cell line(HET-1 A)and in four human esophageal squamous cell carcinoma cell lines(KYSE-510,EC-109,TE-1,TE-13).The expression levels in five cell lines were compared and classified accordingly.3.In four kinds of cancer cells to interfere with or over-expression of DEPTOR,we measured cell proliferation;In the four kinds of cancer cells in different concentrations of different drug treatment,we observed the numbers of cell survival;After four kinds of cancer cells knockdown or overexpression,add the drug treatment to study the effet of DEPTOR expression on cell sensitivity to chemotherapy.4.Explore the potential mechanism of DEPTOR's effect on esophageal cancer cell lines by Western Blot.ConclusionsDEPTOR expression in esophageal squamous cell carcinoma tissues is higher than normal tissues,its existence is conducive to good survival of early stage patients.The four ESCC cell lines expressed higher levels of DEPTOR than the HET-1 A cell lines and expressed differently.Therefore,the four ESCC cell lines were divided into relatively low DEPTOR expression group and relatively high DEPTOR expression group.In the relatively low expression of DEPTOR,DEPTOR plays a role of promoting apoptosis and increasing the sensitivity of cells to chemotherapeutic drugs.In the relatively high expression of DEPTOR,DEPTOR inhibits the apoptosis and decreases the chemosensitivity of cells.DEPTOR inhibits the mTOR-AKT pathway in the relatively low-expression group of DEPTOR;in the relatively high-expression group of DEPTOR,DEPTOR inhibits the mTOR-S6K1 pathway,increases the expression of IRS-1,and negatively activates the PI3K-AKT pathway.