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J Biol Chem. 2016 Jun 24;291(26):13715-29. doi: 10.1074/jbc.M115.703959. Epub 2016 Apr 25.

RhoC GTPase Is a Potent Regulator of Glutamine Metabolism and N-Acetylaspartate Production in Inflammatory Breast Cancer Cells.

Author information

1
From the Departments of Internal Medicine, Molecular and Integrative Physiology, and.
2
From the Departments of Internal Medicine.
3
the Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305.
4
the Department of Medicine, University of Wisconsin, Madison, Wisconsin 53705, and the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
5
Pharmacology, University of Michigan, Ann Arbor, Michigan 48109.
6
Molecular and Integrative Physiology, and.
7
From the Departments of Internal Medicine, smerajve@umich.edu.

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.

KEYWORDS:

N-acetylaspartate; Rho (Rho GTPase); breast cancer; glutamine; hypoxia-inducible factor (HIF); tumor metabolism

PMID:
27129239
PMCID:
PMC4919454
DOI:
10.1074/jbc.M115.703959
[Indexed for MEDLINE]
Free PMC Article

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