Lipid Droplet-Associated Factors, PNPLA3, TM6SF2, and HSD17B Proteins in Hepatopancreatobiliary Cancer

SIMPLE SUMMARY: Aberrant lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of pancreatic and liver cancer. Most cells store fatty acids in the form of triacylglycerols in lipid droplets. Lipid droplets are intracellular organelles that not only store neutral lipids, but also play roles as molecular messengers and signaling factors. Some cancer cells accumulate massive amount of lipid droplets. Lipid droplets and lipid droplet-associated factors are further implicated to mediate proliferation, invasion, metastasis, as well as chemotherapy resistance in several types of cancer. This review dissected recent findings on the role of several lipid droplet-associated factors, patatin-like phospholipase domain-containing 3 (PNPLA3), Transmembrane 6 superfamily member 2 (TM6SF2), and 17β-hydroxysteroid dehydrogenase (HSD17B) 11 and 13 as well as their genetic variations in hepatopancreatobiliary diseases, especially cancer. ABSTRACT: Pancreatic and liver cancer are leading causes of cancer deaths, and by 2030, they are projected to become the second and the third deadliest cancer respectively. Cancer metabolism, especially lipid metabolism, plays an important role in progression and metastasis of many types of cancer, including pancreatic and liver cancer. Lipid droplets are intracellular organelles that store neutral lipids, but also act as molecular messengers, and signaling factors. It is becoming increasingly evident that alterations in the regulation of lipid droplets and their associated factors influence the risk of developing not only metabolic disease but also fibrosis and cancer. In the current review article, we summarized recent findings concerning the roles of lipid droplet-associated factors, patatin-like phospholipase domain-containing 3, Transmembrane 6 superfamily member 2, and 17β-hydroxysteroid dehydrogenase 11 and 13 as well as genetic variants in pancreatic and hepatic diseases. A better understanding of cancer type- and cell type-specific roles of lipid droplet-associated factors is important for establishing new therapeutic options in the future.