Abstract
Simple SummaryMetabolic reprogramming is gaining attentions as a hallmark of cancers. However, lipid metabolism has been difficult to analyze due to technical problems. In recent years, lipidomics techniques such as mass spectrometry have advanced and allowed us to analyze detailed lipid profiles of cancers. Moreover, it has become clear that changes in lipid metabolism also play an important role in the interaction between the cancers and the surrounding microenvironment. This review summarizes the latest research progress of reprogrammed lipid metabolism and also lipidomics technologies applied in cancer research.Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called “lipid metabolic reprogramming”, can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.
Highlights
Introduction iationsLipids consist of numerous water-insoluble molecules and are mainly classified as fatty acids, triacylglycerides, phospholipids, or cholesterol
Glioblastoma cells store excess Fatty acids (FAs) into triglycerides and lipid droplets (LDs) by upregulating diacylglycerol-acyltransferase 1 (DGAT1), and inhibition of DGAT1 promotes glioblastoma cell death through excessive fatty acid oxidation (FAO)-mediated reactive oxidative species (ROS) production [53]. These findings suggest that the role of FAO in carcinogenesis varies depending on cancer type and the surrounding microenvironment
Cancer research has mainly focused on genetic mutations and their expression changes
Summary
Fatty acids (FAs) are important as the basic backbone of many lipids. The de novo FA synthesis pathway converts citrate to palmitic acid through sequential enzymatic reactions catalyzed by ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN). Lipid uptake is conducted through membrane-associated transport proteins, including fatty acid transport protein-1 (FATP1), fatty acid translocase (CD36), and liver fatty acid-binding protein (L-FABP). The expression of these enzymes related to FA metabolism are mainly regulated by sterol regulatory element-binding protein. In the fatty acid oxidation (FAO) process, the rate-limiting step is the translocation of acyl-CoA across the mitochondrial membrane. Through this translocation, acyl-CoA is first converted to acylcarnitine via its conjugation to carnitine by carnitine palmitoyltransferase 1 (CPT1). Acyl-CoA enters the FAO pathway and is followed by the tricarboxylic acid (TCA) cycle (Figure 1)
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