Metabolic Profiling Reveals PAFAH1B3 as a Critical Driver of Breast Cancer Pathogenicity

Many studies have identified metabolic pathways that underlie cellular transformation, but the metabolic drivers of cancer progression remain less well understood. The Hippo transducer pathway has been shown to confer malignant traits on breast cancer cells. In this study, we used metabolic mapping platforms to identify biochemical drivers of cellular transformation and malignant progression driven through RAS and the Hippo pathway in breast cancer and identified platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) as a key metabolic driver of breast cancer pathogenicity that is upregulated in primary human breast tumors and correlated with poor prognosis. Metabolomic profiling suggests that PAFAH1B3 inactivation attenuates cancer pathogenicity through enhancing tumor-suppressing signaling lipids. Our studies provide a map of altered metabolism that underlies breast cancer progression and put forth PAFAH1B3 as a critical metabolic node in breast cancer. [Display omitted] •We have performed a metabolic profiling study to identify drivers of breast cancer•Cancer metabolism is regulated by RAS and Hippo pathways•PAFAH1B3 is a driver of breast cancer•PAFAH1B3 is a metabolic target for breast cancer therapy Using metabolic mapping approaches, Mulvihill et al. identify PAFAH1B3 as a driver of cellular transformation and malignant progression in breast cancer. The enzyme taps into the RAS and Hippo pathways and regulates the landscape tumor-suppressing lipids.