The Long Chain Acyl-coenzyme A Synthetase Family and Malignant Tumors / 中国生物化学与分子生物学报

ABSTRACT

Disorders of the fatty acid metabolism can lead to cancer. The long chain acyl-coenzyme A synthetase (ACSL) family is important in fatty acid metabolism and is responsible for activating long chain fatty acids. In cancer cells, the regulatory effect of ACSLs is often disrupted, and the distribution, type, and quantity of fatty acids are altered. These alterations can lead to cancer development and other metabolic diseases. ACSLs include five subtypes in mammals, namely ACSL1, 3, 4, 5, and 6. ACSL1 is important in the synthesis and distribution of triglycerides. ACSL3 contributes to the formation of lipid droplets, which are important for maintaining lipid homeostasis. The expression of ACSL4 is related to steroid hormones and plays an important role in ferroptosis. ACSL5 can catalyze the metabolism of exogenous fatty acids but not the metabolism of de novo fatty acids. ACSL6 is important in fatty acid metabolism in the brain, spermatogenesis, and ovary. The regulatory factors of ACSLs include transcription factors, coactivators, hormone receptors, protein kinases, and small non-coding RNAs. These factors regulate mitochondria-mediated energy metabolism, endoplasmic reticulum stress, and the tumor inflammatory microenvironment through fatty acid metabolism. In addition, ACSLs serve as independent prognostic factors, biomarkers for clinical diagnosis, and therapeutic targets for various cancers. In recent years, accumulating evidence has demonstrated the important roles of ACSLs in the occurrence and development of cancer. This article focuses on the ACSL family, the relationship between ACSL and malignant tumors, and tumor therapies based on lipid metabolism by ACSLs. The information provides a theoretical basis for the further study of the ACSL family as molecular candidates for the targeted therapy of tumors.