Cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT) plays a key role in antioxidant defense by mediating cystine uptake

promoting glutathione synthesis

and maintaining cell survival under oxidative stress conditions. Recent studies showed that

to prevent toxic buildup of highly insoluble cystine inside cells

cancer cells with high expression of SLC7A11 (SLC7A11

high

) are forced to quickly reduce cystine to more soluble cysteine

which requires substantial NADPH supply from the glucose-pentose phosphate pathway (PPP) route

thereby inducing glucose- and PPP-dependency in SLC7A11

high

cancer cells. Limiting glucose supply to SLC7A11

high

cancer cells results in significant NADPH “debt”

redox “bankruptcy”

and subsequent cell death. This review summarizes our current understanding of NADPH-generating and -consuming pathways

discusses the opposing role of SLC7A11 in protecting cells from oxidative stress–induced cell death such as ferroptosis but promoting glucose starvation–induced cell death

and proposes the concept that SLC7A11-mediated cystine uptake acts as a double-edged sword in cellular redox regulation. A detailed understanding of SLC7A11 in redox biology may identify metabolic vulnerabilities in SLC7A11

high

 cancer for therapeutic targeting.