Fatty acid metabolism and prospects for targeted therapy of cancer

Abstract

Fatty acids are fundamental substrates required for energy storage, synthesis of membranes, generation of signaling molecules and lipid droplet formation in cancer cells. High levels of fatty acid metabolic activity are one of the most aberrant metabolic alterations in cancer cells. The de novo fatty acid synthesis pathway is the primary source of fatty acids in cancer cells, but cancer cells can also acquire fatty acids through the lipolytic pathway, which helps cells survive and maintain their invasiveness. Key enzymes, including ATP‐citrate lyase (ACLY), fatty acid synthase (FASN), acetyl‐coenzyme A (CoA) carboxylase (ACC), stearoyl‐CoA desaturase 1(SCD1) and monoacylglycerol lipase (MAGL), which are involved in fatty acid synthesis and degradation, are overexpressed in cancer cells. The alterations in fatty acid metabolomics in different cancers, at different stages of cancer, and in different tissues are clinically significant. This review focuses on current research into fatty acid metabolism to explore new targets against the fatty acid metabolic pathways for anticancer therapy. Practical applications: High levels of fatty acid metabolic activity are one of the most aberrant metabolic alterations in cancer cells. Reprogramming in fatty acid metabolism plays an important role in energy storage, membrane proliferation, the generation of signaling molecules and lipid droplet formation in cancer cells. Understanding the mechanism of regulated the fatty acid metabolic pathways in cancer would reveal novel targeted therapy of cancer. To maintain the balance of the free fatty acid composition and thus promote cancer cell growth, survival, and progression, the levels of de novo fatty acid synthesis and degradation are elevated. Therefore, the targeted inhibition of key enzymes involved in fatty acid metabolism, such as ACLY, ACC, FASN, MAGL, and SCD1, and the utilization of anticancer exogenous fatty acids might constitute effective cancer therapies. ATP, adenosine‐triphosphate; DAG, diacylglycerol; IHBTIS, inhibitors; MUFA, monounsaturated fatty acids; MAG, monoacylglycerol; TAG triacylglycerol.

Spatially resolved metabolomics to discover tumor-associated metabolic alterations

“…Overall, the FA ion intensities demonstrated an increasing trend from muscle to epithelium to cancer tissue in ESCC. It has been reported that cancer cells rapidly produce FAs to meet the urgent need for membrane biosynthesis, cellular signaling, and energy consumption (3, 39). In the FA biosynthesis pathway, FASN is a key metabolic enzyme for the de novo synthesis of FAs.…”

Biomolecular Component Analysis of Phospholipids Composition in Live HeLa Cells

“…It was also reported by other groups that the increasing amount of saturated fatty acids within the liver provokes endoplasmic reticulum stress, apoptosis, and liver injury [14,15]. Therefore, nowadays, fatty acid metabolic pathways are often considered as a target for anticancer therapy [16,17]. Moreover, alteration of polyunsaturated fatty acid levels and the signaling pathways that they regulate also was detected in various neurological disorders (e.g., Alzheimer’s disease and major depression) [4,5].…”

Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma

“…Fatty acids (FAs) are critical endogenous molecules for cellular energy storage, membrane formation, and signal transmission. It has been reported that upregulation of fatty acid synthesis is one of the most aberrant metabolic features of tumors and is required for membrane proliferation, energy consumption, lipid droplet formation, and signaling generation in various cancers ( Chen and Li, 2017 ). The ion intensities of several FAs were found to be an increasing trend from the muscle to the epithelium to cancer tissue in ESCC, which was in good agreement with the expression of FASN, a critical metabolic enzyme for the de novo synthesis of FAs ( Sun et al, 2019 ).…”