Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR-α signaling

• Published in: Journal of lipid research Vol. 60; no. 11; pp. 1807 - 1817
• Main Authors: Kwong, Soke Chee, Jamil, Amira Hajirah Abd, Rhodes, Anthony, Taib, Nur Aishah, Chung, Ivy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2019; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: cancer; Cell Death; fatty acid binding protein; fatty acid metabolism; Fatty Acid-Binding Protein 7 - metabolism; Female; Humans; metabolic adaptation; nutrient deprivation; peroxisome proliferator-activated receptor alpha; PPAR alpha - metabolism; Signal Transduction; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumor Cells, Cultured; Tumor Suppressor Proteins - metabolism; fatty acid binding protein; cancer; metabolic adaptation; peroxisome proliferator-activated receptor alpha; nutrient deprivation; fatty acid metabolism
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M092379

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high-energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentiviral particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231, cells. FABP7-overexpressing Hs578T (Hs-FABP7) cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling.