Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer.

Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer.
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DOI:
10.1186/s40880-018-0288-x
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发表时间:
2018-04-25
期刊:
Cancer communications (London, England)
影响因子:
--
通讯作者:
Gan B
Gan B
中科院分区:
其他
文献类型:
--
作者:
Koppula P;Zhang Y;Zhuang L;Gan B

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癌细胞经常上调营养转运蛋白,以满足其增加的生物合成和生物能量需求,并维持氧化还原动态平衡。一种经常在人类癌症中过度表达的营养转运蛋白是胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(SLC7A11;也称为XCT)。SLC7A11促进胱氨酸摄取和谷胱甘肽的生物合成,从而保护细胞免受氧化应激和铁链细胞死亡的影响。最近的研究意外地发现SLC7A11也在谷氨酰胺代谢中发挥关键作用,并调节癌细胞对葡萄糖和谷氨酰胺的依赖。这篇综述讨论了SLC7A11在调节癌细胞的抗氧化反应和营养依赖性中的作用,探索了我们对SLC7A11在癌症代谢中的调控的理解,并强调了在这一新兴研究领域中未来研究的关键开放问题。更深入地了解SLC7A11在癌症代谢中的作用,可能会发现针对这种重要的氨基酸转运体进行癌症治疗的新的治疗机会。
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs, and to maintain redox homeostasis. One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT). SLC7A11 promotes cystine uptake and glutathione biosynthesis, resulting in protection from oxidative stress and ferroptotic cell death. Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells. This review discusses the roles of SLC7A11 in regulating the antioxidant response and nutrient dependency of cancer cells, explores our current understanding of SLC7A11 regulation in cancer metabolism, and highlights key open questions for future studies in this emerging research area. A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
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