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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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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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