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...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。展开更多
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 cancers.Recent studies reveal...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 cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,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) 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.展开更多
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 i...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 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.展开更多
Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular lives.Incorporation of these components into cellular processes,however,comes at a ...Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular lives.Incorporation 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).展开更多
基金Andrew Sabin Family Fellow Award和Institutional Research Grant from the University of Tex as MD Anderson Cancer Center,Grants from National Institutes of Health(CA181196和CA190370)Anna Fuller Fund和Ellison Medical Foundation(AGNS-0973-13)的资助
文摘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。
基金The research in authors'lab has been supported by The University of Texas MD Anderson Cancer Center,KC180131 from Department of Defense Kidney Cancer Research Program,R01CA181196,R01CA190370,R01CA244144 from the National Institutes of Health(to BG)CPRIT Research Training Grant(RP170067)Dr.John J.Kopchick Research Award from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences(to PK).
文摘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 cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,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) 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.
基金supported by the Andrew Sabin Family Fellow Award and Institutional Research Grant from the University of Texas MD Anderson Cancer Center,Grants from National Institutes of Health(CA181196 and CA190370)Anna Fuller Fund,and Ellison Medical Foundation(AG-NS-0973-13).
文摘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 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.
基金Research in the authors'lab has been supported by The University of Texas MD Anderson Cancer Center,National Institutes of Health grants R01CA181196,R01CA190370,R01CA244144,and R01CA247992(to BG)a CPRIT Research Training Grant(RP170067)+1 种基金the Dr.John J.Kopchick Research Award from The Un iversity of Texas MD Anders on Cancer Center UTHealth Graduate School of Biomedical Sciences(to PK)This work was also supported in part by Cancer Center Support(Core)Grant P30 CA016672 from the National Cancer Institute,to The University of Texas MD Anderson Cancer Center.
文摘Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular lives.Incorporation 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).