Fatty acid-binding protein 5 (FABP5) promotes lipolysis of lipid droplets, de novo fatty acid (FA) synthesis and activation of nuclear factor-kappa B (NF-κB) signaling in cancer cells

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2018-09, Vol.1863 (9), p.1057-1067
• Main Authors: Senga, Shogo, Kobayashi, Narumi, Kawaguchi, Koichiro, Ando, Akira, Fujii, Hiroshi
• Format: Article
• Language: English
• Subjects: Acetyltransferases - genetics; Acetyltransferases - metabolism; Cancer; Cell Line, Tumor; Coenzyme A Ligases - genetics; Coenzyme A Ligases - metabolism; Cytokines - genetics; Cytokines - metabolism; FABP5; Fatty acid metabolism; Fatty Acid-Binding Proteins - antagonists & inhibitors; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Fatty Acids - biosynthesis; Female; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Lipid droplet; Lipid Droplets - chemistry; Lipid Droplets - metabolism; Lipolysis; Male; Mammary Glands, Human - metabolism; Mammary Glands, Human - pathology; Monoacylglycerol Lipases - genetics; Monoacylglycerol Lipases - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Prostate - metabolism; Prostate - pathology; Protein Kinase C - genetics; Protein Kinase C - metabolism; Reactive Oxygen Species - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Sterol Esterase - genetics; Sterol Esterase - metabolism
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2018.06.010

Fatty acid-binding proteins (FABPs) are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting them to the appropriate compartments in the cell. Epidermal fatty acid-binding protein (FABP5) is an intracellular lipid-binding protein that is abundantly expressed in adipocytes and macrophages. Previous studies have revealed that the FABP5 expression level is closely related to malignancy in various types of cancer. However, its precise functions in the metabolisms of cancer cells remain unclear. Here, we revealed that FABP5 knockdown significantly induced downregulation of the genes expression, such as hormone-sensitive lipase (HSL), monoacylglycerol lipase (MAGL), elongation of long-chain fatty acid member 6 (Elovl6), and acyl-CoA synthetase long-chain family member 1 (ACSL1), which are involved in altered lipid metabolism, lipolysis, and de novo FA synthesis in highly aggressive prostate and breast cancer cells. Moreover, we demonstrated that FABP5 induced inflammation and cytokine production through the nuclear factor-kappa B signaling pathway activated by reactive oxygen species and protein kinase C in PC-3 and MDA-MB-231 cells. Thus, FABP5 might regulate lipid quality and/or quantity to promote aggressiveness such as cell growth, invasiveness, survival, and inflammation in prostate and breast cancer cells. In the present study, we have revealed for the first time that high expression of FABP5 plays a critical role in alterations of lipid metabolism, leading to cancer development and metastasis in highly aggressive prostate and breast cancer cells. •FABP5 promotes lipolysis of lipid droplets in prostate and breast cancer cells.•FABP5 up-regulates expression of lipolysis- and de novo FA synthesis-related genes.•Activation of PKC and increase in ROS levels by FABP5 induces NF-κB signaling.•NF-κB activated by FABP5 promotes gene expression involved in cancer development.