Abstract
Simple SummaryAberrant 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.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.
Highlights
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
lipid droplets (LDs)-associated proteins play an important role in dynamics of LD and it is evident that expression or genetic variation of several
LD-associated factors are associated with overall survival in pancreatic cancer patients
Summary
Pancreatic cancer is currently the fourth leading cause of cancer deaths in the United. The precise role of each AGPAT family member in AGPAT9 expression is associated with significantly shorter overall survival of c hepatopancreatobiliary cancer has not been clarified. A deficiency in the lipolytic enzyme PNPLA2 may promote pancreatic steatosis by inducing an imbalance in TAG turnover and an increase in the storage of LDs [31]. Another study showed that high expression of PNPLA2 is associated with adiposity and increased tumor stroma in patients with pancreatic cancer [36]. Cancers 2021, 13, x FOR PEER REVIEW activity of PNPLA2 by HILPDA leads to inhibition of lipolysis, attenuated fatty acid oxidation and reactive oxygen species (ROS) production. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HCC: Hepatocellular carcinoma; HSD: Hydroxysteroid; LD: Lipid droplet; NAFLD: Nonalcoholic steatohepatitis; PNPLA: Patatin-like phospholipase; RDH: Retinol dehydrogenase; TAG: Triacylglycerol; TM6SF2: Transmembrane 6 superfamily member 2
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