The Role of Fatty Acid Metabolism in Estrogen Receptor-Negative Breast Cancer

Abstract

Abstract : The goal of this project is to investigate the role of long chain fatty acyl-CoAsynthetase 4 (ACSL4) as a biomarker for, and mediator of an aggressive breast cancer phenotype. Results indicate that expression of ACSL4 in breast cell lines and tumor samples is inversely correlated with expression of estrogen receptor, progesterone receptor, androgen receptor and human epidermal growth factor receptor 2 (HER2). Breast cancer lacking all 4receptors (quadruple negative breast cancer (QNBC)) can be identified by ACSL4 expression status with a sensitivity of 78 and a specificity of 86 . In addition, in vitro data from experiments in breast cancer cell lines demonstrates that simultaneous expression of a receptor and ACSL4 is characterized by resistance to treatment with a receptor-based targeted therapy, such as tamoxifen or lapatinib. Forced expression of ACSL4 results in increased proliferation, migration and invasion. The effects are specific for ACSL4 in that neither a mutant ACSL4 lacking enzyme activity nor ACSL3 are effective. Messenger RNA and protein expression data indicate possible effectors of the action of ACSL4.