MOGAT2 influence colorectal cancer progression through ACSM1-mediated lipid metabolic reprogramming

Monoacylglycerol O-acyltransferase 2 (MOGAT2) plays a significant role in influencing colorectal cancer (CRC) progression by regulating lipid metabolism through ACSM1 (Acyl-CoA synthetase medium-chain family member 1). In a study investigating MOGAT2’s role, researchers found that its expression directly impacts tumor behavior. When MOGAT2 was suppressed, CRC cells exhibited aggressive characteristics, including increased proliferation, invasion, and colony formation, along with reduced apoptosis (cell death). These changes suggest a more malignant cancer phenotype. On the other hand, overexpressing MOGAT2 reversed these effects, reducing tumor growth and invasion, promoting apoptosis, and inhibiting epithelial-mesenchymal transition (EMT), a process critical for cancer metastasis.

Mechanistically, MOGAT2 reprograms lipid metabolism in CRC cells. It reduces the accumulation of free fatty acids, regulates cholesterol transport, and suppresses the expression of lipid synthesis enzymes like GPAT2, GPAT3, and GAAT. This reprogramming helps restore metabolic balance in cancer cells, which is crucial for controlling their growth and spread.

Further analysis identified ACSM1 as a key downstream mediator of MOGAT2’s tumor-suppressive effects. ACSM1 contributes to the metabolic changes induced by MOGAT2. When ACSM1 was silenced, the beneficial effects of MOGAT2 overexpression were lost, and cancer cells regained aggressive traits, reduced apoptosis, and experienced metabolic dysregulation.

In summary, MOGAT2 acts as a tumor suppressor in CRC by modulating lipid metabolism through ACSM1. This pathway reduces tumor growth, promotes apoptosis, and inhibits invasion and EMT. Targeting the MOGAT2–ACSM1 axis may offer a promising therapeutic approach for managing CRC progression.