Cystine transporter SLC7A11/xCT in cancer:ferroptosis,nutrient dependency,and cancer therapy |
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| Authors: | Pranavi Koppula Li Zhuang Boyi Gan |
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| Institution: | 1.Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA ;2.The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX USA |
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| Abstract: | The cystine/glutamate antiporter SLC7A11 (also com-monly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression pro-motes tumor growth partly through suppressing fer-roptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11 (SLC7A11high) also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11high cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11high cancer.In 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 treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies. |
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| Keywords: | SLC7A11 xCT cystine cysteine ferroptosis nutrient dependency cancer therapy |
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