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

LuikaA Timmerman, Thomas Holton, Mariia Yuneva, RaymondJ Louie, Mercè Padró, Anneleen Daemen, Min Hu, DeniseA Chan, StephenP Ethier, LauraJ van'tVeer, Kornelia Polyak, Frank McCormick, Joe Gray

Research output: Contribution to journalArticle

206 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
Publication statusPublished - Oct 14 2013

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ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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