Alterations in metabolism have been defied as hallmarks of human cancers. One of the most well-studied metabolic change in cancer cells is altered lipid metabolism, mainly characterized by increased fatty acid synthesis (FAS), which provides building blocks, signaling molecules and storage compounds for cancer cell proliferation [1,2]. Although most researchers on lipid metabolism reprogramming focuses on increased FA synthesis, the role of fatty acid oxidation (FAO) in cancer is not well examined [3]. FAO not only provide ATP for rapid cell proliferation, but also provide NADPH production to maintain redox homeostasis. However, very little is known about the molecular players that regulate FAO in cancer cells.

Acetyl-CoA carboxylases (ACCs) are rate-limiting enzymes in fatty acid metabolism through catalyzing the carboxylation of acetyl-CoA to malonyl-CoA, which functions as both intermediate of FAS and inhibitor of FAO [4]. There are two isoforms of ACCs, including ACC1 (also termed ACCα) localized in cytoplasm and ACC2 (also termed ACCβ) localized in mitochondria [5]. Cytosolic ACC1 provides malonyl-CoA for FAS, while the malonyl-CoA produced by ACC2 suppresses FAO by inhibiting the mitochondrial outer membrane-localized carnitine palmitoyltransferase 1 (CPT-1), which converts long-chain acyl-CoA species to their corresponding long-chain acyl-carnitines for transport into mitochondria [6]. Previously, most studies focused on the role of ACC1-regulated FAS in tumor development and progression, while the function of ACC2-regulated FAO remains largely uncharacterized in human cancers [7], especially in ovarian cancer (OC).

In the present study, the expression, clinical significance and biological functions of ACC2 were systematically evaluated in OC. In addition, the mechanism underlying the abnormal expression of ACC2 in OC was also explored in depth.