title: Metabolic profiling reveals PAFAH1B3 as a critical driver of breast cancer pathogenicity.
abstract: 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.
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Melinda M
authors: MM
authors: Mulvihill
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Daniel I
authors: DI
authors: Benjamin
authors: Department of Molecular and Cell Biology, University of California, Berkeley, GL41 Koshland Hall, Berkeley, CA 94720, USA.
authors: Xiaodan
authors: X
authors: Ji
authors: Department of Molecular and Cell Biology, University of California, Berkeley, GL41 Koshland Hall, Berkeley, CA 94720, USA.
authors: Erwan
authors: E
authors: Le Scolan
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Sharon M
authors: SM
authors: Louie
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Alice
authors: A
authors: Shieh
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: McKenna
authors: M
authors: Green
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Tara
authors: T
authors: Narasimhalu
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA.
authors: Patrick J
authors: PJ
authors: Morris
authors: Department of Molecular and Cell Biology, University of California, Berkeley, GL41 Koshland Hall, Berkeley, CA 94720, USA.
authors: Kunxin
authors: K
authors: Luo
authors: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 127 Morgan Hall, Berkeley, CA 94720, USA. Electronic address: dnomura@berkeley.edu.
authors: Daniel K
authors: DK
authors: Nomura
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D006801:Humans; D055432:Metabolomics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D040901:Proteomics
chemical_list: D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C523923:PAFAH1B2 protein, human; C568468:PAFAH1B3 protein, human