Cystine-glutamate antiporter (System xc-) (xCT or SLC7A11/SLC3A2)

The **cystine-glutamate antiporter (System xc-)** is a heterodimeric membrane transporter composed of the light chain SLC7A11 (xCT) and the heavy chain SLC3A2. It belongs to the heteromeric amino acid transporter family (SLC7) and functions as a Na+-independent, chloride-dependent, 1:1 antiporter, exchanging extracellular cystine for intracellular glutamate across the plasma membrane[4][7][2][3]. Imported cystine is reduced to cysteine, the rate-limiting precursor for the synthesis of the antioxidant glutathione (GSH), supporting cellular redox homeostasis and protecting against oxidative stress[4][2][8]. System xc- is overexpressed in numerous cancers, contributing to tumor growth, resistance to therapy, and adaptation to oxidative environments, thus serving as a promising therapeutic target in oncology and neuroprotection[9][8][2][5]. Due to its role in nonvesicular release of glutamate, it also influences neurotransmission and excitotoxicity in the central nervous system. Pharmacological inhibition of this transporter can trigger oxidative stress-induced cell death (ferroptosis), but chronic blockade may risk CNS toxicity or impaired immune function[4][5][9].

Other names

System xc-xCTSLC7A11/SLC3A2 heterodimerCystine/glutamate transporterCystine/glutamate exchanger

Competitive inhibition of cystine uptake (e.g., sulfasalazine, erastin block transporter) Induction of ferroptosis by preventing cystine import and GSH synthesis (e.g., erastin, sorafenib) Modulation of extracellular glutamate concentration (affecting excitotoxicity/neurotransmission)