Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target

Cancer Cell. 2013 Oct 14;24(4):450-65. doi: 10.1016/j.ccr.2013.08.020. Epub 2013 Oct 3.


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 in vivo. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System y+ / metabolism*
  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glutamine / metabolism
  • Glutamine / pharmacology*
  • Glutathione / metabolism
  • Humans
  • Mice
  • Prognosis
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species
  • Triple Negative Breast Neoplasms / metabolism*


  • Amino Acid Transport System y+
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • SLC7A11 protein, human
  • Slc7a11 protein, mouse
  • Glutamine
  • Glutathione

Associated data

  • GEO/GSE48984