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

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 13C tracer experiments, we fo...

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Bibliographic Details
Published in:The Journal of biological chemistry 2016-06, Vol.291 (26), p.13715-13729
Main Authors: Wynn, Michelle L., Yates, Joel A., Evans, Charles R., Van Wassenhove, Lauren D., Wu, Zhi Fen, Bridges, Sydney, Bao, Liwei, Fournier, Chelsea, Ashrafzadeh, Sepideh, Merrins, Matthew J., Satin, Leslie S., Schnell, Santiago, Burant, Charles F., Merajver, Sofia D.
Format: Article
Language:English
Subjects:
Aspartic Acid - analogs & derivatives
Aspartic Acid - biosynthesis
Aspartic Acid - genetics
breast cancer
Cell Line, Tumor
Female
glutamine
Glutamine - genetics
Glutamine - metabolism
Humans
hypoxia-inducible factor (HIF)
Inflammatory Breast Neoplasms - genetics
Inflammatory Breast Neoplasms - metabolism
Inflammatory Breast Neoplasms - pathology
Metabolism
N-acetylaspartate
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Rho (Rho GTPase)
rho GTP-Binding Proteins - genetics
rho GTP-Binding Proteins - metabolism
rhoC GTP-Binding Protein
tumor metabolism
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Summary: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 13C 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.703959