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Cystine transporter SLC7A11/xCT in cancer:ferroptosis,nutrient dependency,and cancer therapy

Protein & Cell 2021年第8期12卷 599-620页

作者： pranavi koppula Li Zhuang Boyi Gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human *** studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid ***,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) *** this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer *** review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.

关键词： SLC7A11 xCT cystine cysteine ferroptosis nutrient dependency cancer therapy

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Cytochrome P450 reductase(POR)as a ferroptosis fuel

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Protein & Cell 2021年第9期12卷 675-679页

Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular *** of these components into cellular processes,however,comes at a cost:the bis-allylic structure of PUFAs and the enrichment of cellular environments with iron and oxygen render PUFA-containing phospholipids(PUFA-PLs)particularly susceptible to peroxidation(Yang and Stockwell,2016).

关键词： render Oxygen structure

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

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Cancer Communications 2018年第1期38卷 145-157页

作者： pranavi koppula Yilei Zhang Li Zhuang Boyi Gan Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer Center1515 Holcombe BlvdHoustonTX 77030USA The University of Texas Graduate School of Biomedical Sciences 6767 Bertner Ave.HoustonTX 77030USA Department of Molecular and Cellular Oncology The University of Texas MD

Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox *** 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 *** studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer *** review discusses the roles of SLC7A11 in regulating the anti-oxidant 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.

关键词： SLC7A11 xCT System xc− Cystine Glutamate Ferroptosis Oxidative stress Nutrient dependency Cancer metabolism

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位于氧化还原稳态调控和癌症营养依赖性十字路口的氨基酸转运蛋白SLC7A11/xCT

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癌症 2018年第10期37卷 425-438页

作者： pranavi koppula Yilei Zhang Li Zhuang Boyi Gan Department of Experimental Radiation Oncology The University of TexasMD Anderson Cancer Center 1515 Holcombe Blvd Houston TX 77030USA The University of Texas Graduate School of Biomedical Sciences 6767 Bertner Ave. Houston TX 77030 USA Department of Molecular andCellular Oncology The University of Texas MD Anderson Cancer Center1515 Holcombe Blvd Houston TX 77030 USA.

癌细胞经常会上调营养转运蛋白的表达,以满足它们日益增加的生物合成和生物能量需求,并维持氧化还原的动态平衡。在人类癌症中有一种经常过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(solute carrier family 7... 详细信息

癌细胞经常会上调营养转运蛋白的表达,以满足它们日益增加的生物合成和生物能量需求,并维持氧化还原的动态平衡。在人类癌症中有一种经常过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(solute carrier family 7 member 11,SLC7A11,也称为xCT)。SLC7A11促进胱氨酸摄取和谷胱甘肽生物合成,从而防止氧化应激和细胞铁死亡。最近的研究意外地揭示了SLC7A11在谷氨酰胺代谢中也起着关键作用,并调节癌细胞的葡萄糖和谷氨酰胺依赖性。本文综述了SLC7A11在调节癌细胞抗氧化反应和营养依赖中的作用,探讨了SLC7A11在肿瘤代谢中的调控作用,并提出了这一新兴研究领域中有待进一步研究的关键问题。对癌症代谢中SLC7A11的更深入了解可能会为这种重要的氨基酸转运蛋白靶向癌症治疗提供新的治疗机会。

关键词： SLC7A11 xCT xc-系统胱氨酸谷氨酸铁死亡氧化应激营养依赖癌症代谢

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