Document Type

Article

Journal Title

PLoS One

Publication Date

2017

Volume

12

Abstract

BACKGROUND: Mucin1 (MUC1), a glycoprotein associated with chemoresistance and an aggressive cancer phenotype, is aberrantly overexpressed in triple-negative breast cancer (TNBC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism and thereby supports tumor growth. Herein, we examined the role of MUC1 in metabolic reprogramming in TNBC.

METHODS: MUC1 was stably overexpressed in MDA-MB-231 TNBC cells and stably knocked down in MDA-MB-468 cells. We performed liquid chromatography-coupled tandem mass spectrometry-assisted metabolomic analyses and physiological assays, which indicated significant alterations in the metabolism of TNBC cells due to MUC1 expression.

RESULTS: Differential analyses identified significant differences in metabolic pathways implicated in cancer cell growth. In particular, MUC1 expression altered glutamine dependency of the cells, which can be attributed in part to the changes in the expression of genes that regulate glutamine metabolism, as observed by real-time PCR analysis. Furthermore, MUC1 expression altered the sensitivity of cells to transaminase inhibitor aminooxyacetate (AOA), potentially by altering glutamine metabolism.

CONCLUSIONS: Collectively, these results suggest that MUC1 serves as a metabolic regulator in TNBC, facilitating the metabolic reprogramming of glutamine utilization that influences TNBC tumor growth.

MeSH Headings

Cell Line, Tumor, Cell Proliferation, Cell Survival, Cellular Reprogramming, Chromatography, Liquid, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glucose, Glutamine, Humans, Metabolome, Mucin-1, Nitrogen, Real-Time Polymerase Chain Reaction, Tandem Mass Spectrometry, Triple Negative Breast Neoplasms

ISSN

1932-6203

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

S1 Fig.tif (713 kB)
S1 Methods.docx (42 kB)
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S2 Table.docx (112 kB)

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