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.
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
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Goode, Gennifer; Gunda, Venugopal; Chaika, Nina V.; Purohit, Vinee; Yu, Fang; and Singh, Pankaj K., "MUC1 Facilitates Metabolomic Reprogramming in Triple-Negative Breast Cancer" (2017). Journal Articles: Eppley Institute. 36.