Multifaceted regulation and functions of fatty acid desaturase 2 in human cancers

Abstract

As an important hallmark of metabolic reprogramming in cancer, a disruption in fatty acid metabolism contributes to tumor proliferation, cell migration and invasion, and other tumor cell behaviors. In recent years, more and more studies have been conducted on fatty acid desaturase 2 (FADS2), the first rate-limiting enzyme for the biosynthesis of polyunsaturated fatty acids. These studies have found that FADS2 is abnormally expressed in cancers of the breast, lung, liver, and esophagus; melanoma; leukemia; and other malignant tumors. Furthermore, its expression is significantly correlated with tumor proliferation, cell migration and invasion, clonal formation, angiogenesis, ferroptosis, resistance to radiotherapy, histological grade, metastasis to lymph nodes, clinical stage, and prognosis. The abnormal expression of FADS2 results in an imbalance of cell membrane phospholipids, which disrupts the fluidity of the membrane structure and the transmission of signals and promotes the production of proinflammatory factors and arachidonic acid (AA) metabolites, ultimately harming human health. This article aims to systematically review the structural characteristics of FADS2; its function, expression, and mechanism of action; and the factors affecting its activity. This review also provides new ideas and strategies for the development of treatments aimed at the metabolic reprogramming of tumors.

Keywords: Fatty acid desaturase 2; expression; function; human cancer; metabolism.

Figure 1

The structure of human FADS2. The blue area is the cytochrome b5-like domain, the red area is the transmembrane domain, and the green area is the histidine-rich domain (region I, II, and III).

Figure 2

The metabolic pathways catalyzed by FADS2 in organisms (A) and the factors affecting FADS2 activity (B).