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首页> 外文期刊>Cancer Cell >Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target
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Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target

机译：谷氨酰胺敏感性分析确定xCT反转运蛋白是常见的三阴性乳腺癌治疗靶点

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摘要

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.
机译：少数肿瘤来源的细胞系构成癌症治疗发展的主体，产生的药物影响通常以疾病进展数月来衡量。为了开发更有效的乳腺癌治疗剂并更容易理解其临床影响，我们构建了46种独立衍生的乳腺癌细胞系的功能性代谢肖像。我们对谷氨酰胺摄取和依赖性的分析确定了三阴性样品的一部分，即谷氨酰胺营养缺陷型。环境性谷氨酰胺通过xCT反转运蛋白间接支持环境胱氨酸的获取，xCT反转运蛋白在体内三分阴性肿瘤的三分之一中表达。临床认可的消炎性柳氮磺吡啶嗪对xCT的抑制作用会降低肿瘤的生长，揭示预后最差的乳腺肿瘤的治疗靶点以及快速有效开发药物的先导化合物。

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