Yu W, et al. Gen Physiol Biophys 2020.
Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor. Obesity has been confirmed to be closely related to the occurrence of CRC, but the specific mechanism is not clear. This study mainly explored the roles of obesity-related genes, fatty acid synthase (FASN) and zinc-alpha-2-glycoprotein (AZGP1), in CRC. 30 cases of CRC tissues and adjacent normal colorectal tissues were obtained to quantify the levels of FASN and AZGP1 using qRT-PCR and Western blotting.
Overexpression-AZGP1, overexpression-FASN and FASN shRNA were transfected into SW480 cells. CCK-8, wound healing and Transwell assays were used to evaluate the roles of FASN and AZGP1 on cell proliferation, migration as well as invasion. Western blot was performed to investigate the expression of MMP-2, MMP-9 and mTOR signaling-related proteins. AZGP1 expression was decreased in CRC tissues, which was negatively correlated with FASN expression. Overexpression-AZGP1 showed a significant inhibitory effect on cell proliferation, invasion and migration via inhibiting MMP-2 and MMP-9 expressions. Furthermore, up-regulation of AZGP1 suppressed the expression of mTOR pathway downstream proteins 4EBP and eIF4E through inhibiting FASN expression. Reintroduction of overexpression-FASN could partially reverse and inhibition of FASN further decrease the anti-tumor effect of AZGP1. AZGP1 suppresses CRC cellular activities by regulating FASN via mTOR pathway, suggesting that AZGP1 and FASN may be the targets for CRC therapy.