MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer

Gennifer Goode, Venugopal Gunda, Nina V. Chaika, Vinee Purohit, Fang Yu, Pankaj Singh

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere0176820
JournalPloS one
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

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Triple Negative Breast Neoplasms
Metabolomics
metabolomics
Glutamine
Metabolism
breast neoplasms
glutamine
Tumors
metabolism
Aminooxyacetic Acid
neoplasms
Liquid chromatography
Cell growth
Transaminases
Neoplasms
Mass spectrometry
Growth
Assays
Glycoproteins
Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer. / Goode, Gennifer; Gunda, Venugopal; Chaika, Nina V.; Purohit, Vinee; Yu, Fang; Singh, Pankaj.

In: PloS one, Vol. 12, No. 5, e0176820, 01.05.2017.

Research output: Contribution to journalArticle

Goode, Gennifer ; Gunda, Venugopal ; Chaika, Nina V. ; Purohit, Vinee ; Yu, Fang ; Singh, Pankaj. / MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer. In: PloS one. 2017 ; Vol. 12, No. 5.
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