Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target

Luika A. Timmerman, Thomas Holton, Mariia Yuneva, Raymond J. Louie, Mercè Padró, Anneleen Daemen, Min Hu, Denise A. Chan, Stephen P. Ethier, Laura J. van'tVeer, Kornelia Polyak, Frank McCormick, Joe W. Gray

Research output: Contribution to journalArticle

225 Scopus citations

Abstract

A handful of tumor-derived cell lines form the mainstay of cancer therapeutic development, yielding drugs with an impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics and more readily understand their clinical impact, we constructed a functional metabolic portrait of 46 independently derived breast cell lines. Our analysis of glutamine uptake and dependence identified a subset of triple-negative samples that are glutamine auxotrophs. Ambient glutamine indirectly supports environmental cystine acquisition via the xCT antiporter, which is expressed on one-third of triple-negative tumors invivo. xCT inhibition with the clinically approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development.

Original languageEnglish (US)
Pages (from-to)450-465
Number of pages16
JournalCancer Cell
Volume24
Issue number4
DOIs
StatePublished - Oct 14 2013

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van'tVeer, L. J., Polyak, K., McCormick, F., & Gray, J. W. (2013). Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target. Cancer Cell, 24(4), 450-465. https://doi.org/10.1016/j.ccr.2013.08.020