title: RhoC GTPase Is a Potent Regulator of Glutamine Metabolism and N-Acetylaspartate Production in Inflammatory Breast Cancer Cells.
abstract: Inflammatory breast cancer (IBC) is an extremely lethal cancer that rapidly metastasizes. Although the molecular attributes of IBC have been described, little is known about the underlying metabolic features of the disease. Using a variety of metabolic assays, including (13)C tracer experiments, we found that SUM149 cells, the primary in vitro model of IBC, exhibit metabolic abnormalities that distinguish them from other breast cancer cells, including elevated levels of N-acetylaspartate, a metabolite primarily associated with neuronal disorders and gliomas. Here we provide the first evidence of N-acetylaspartate in breast cancer. We also report that the oncogene RhoC, a driver of metastatic potential, modulates glutamine and N-acetylaspartate metabolism in IBC cells in vitro, revealing a novel role for RhoC as a regulator of tumor cell metabolism that extends beyond its well known role in cytoskeletal rearrangement.
authors.affiliation: From the Departments of Internal Medicine, Molecular and Integrative Physiology, and.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wynn
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Yates
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Charles R
authors.identifier: 0000-0001-6698-5330
authors.initials: CR
authors.lastname: Evans
authors.affiliation: the Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Van Wassenhove
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Zhi Fen
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Sydney
authors.initials: S
authors.lastname: Bridges
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Liwei
authors.initials: L
authors.lastname: Bao
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Fournier
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Ashrafzadeh
authors.affiliation: the Department of Medicine, University of Wisconsin, Madison, Wisconsin 53705, and the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
authors.forename: Matthew J
authors.identifier: 0000-0003-1599-9227
authors.initials: MJ
authors.lastname: Merrins
authors.affiliation: Pharmacology, University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Satin
authors.affiliation: Molecular and Integrative Physiology, and.
authors.forename: Santiago
authors.identifier: 0000-0002-9477-3914
authors.initials: S
authors.lastname: Schnell
authors.affiliation: From the Departments of Internal Medicine.
authors.forename: Charles F
authors.identifier: 0000-0001-9189-5003
authors.initials: CF
authors.lastname: Burant
authors.affiliation: From the Departments of Internal Medicine, smerajve@umich.edu.
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005973:Glutamine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D009363:Neoplasm Proteins; D005973:Glutamine; D001224:Aspartic Acid; C000179:N-acetylaspartate; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
keywords: N-acetylaspartate; Rho (Rho GTPase); breast cancer; glutamine; hypoxia-inducible factor (HIF); tumor metabolism