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Description

Cystine/glutamate transporter (UniProt: Q9UPY5, also known as Amino acid transport system xc-, Calcium channel blocker resistance protein CCBR1, Solute carrier family 7 member 11, xCT) is encoded by the SLC7A11 gene (Gene ID: 23657) in human. xCT is a multi-pass membrane protein with seven cytoplasmic domains, twelve transmembrane domains, and six extracellular domains. It serves as a sodium-independent, high-affinity exchange of anionic amino acids and has high specificity for anionic form of cystine and glutamate. Its expression is induced in response to reactive oxygen species (ROS)-inducing agents such as hydrogen peroxide, leading to enhanced glutathione (GSH) production. Higher expression of xCT is reported in astrocytes where it acts as an antiporter that couples the uptake of one molecule of cystine with the export of one molecule of glutamate. It is overexpressed in several cancers, including non-small cell lung cancer, breast cancer, and liver cancer and its elevated levels are associated with poor outcome. It has also been implicated in promoting tumorigenesis through its antioxidant function that supports cancer cell proliferation, matrix invasion, and tumor growth. Normally, KRAS is shown to protect fibroblasts against oxidative damage by stimulating xCT to enhance glutathione levels. However, in cancer cells xCT expression and activity can be induced by mutant KRAS, which can favor tumor growth. (Ref.: Lim, JKM., et al. (2019). Proc. Natl. Acad. Sci. USA. 116(19), 9433-9442).