Solute carrier family 7 member 11 (SLC7A11) (SLC7A11)

The System xc- transporter, primarily defined by its functional light-chain subunit Solute carrier family 7 member 11 (SLC7A11), is a sodium-independent amino acid antiporter that mediates the stoichiometric exchange of extracellular cystine for intracellular glutamate [1, 5, 14]. Once imported, cystine is rapidly reduced to cysteine, the rate-limiting precursor for the synthesis of glutathione (GSH), which is the cell's most vital antioxidant [4, 13, 16]. This process is essential for maintaining cellular redox homeostasis and preventing ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation [2, 5, 10]. SLC7A11 is frequently overexpressed in various malignant tumors, including breast, lung, and glioma, where it supports high antioxidant demands and promotes resistance to chemotherapy and radiotherapy [1, 3, 12]. Pharmacological inhibition of this transporter using agents like erastin or sulfasalazine is a key strategy for inducing ferroptotic cell death in resistant cancers [2, 11]. Beyond oncology, System xc- is involved in neurodegenerative disorders and addiction through its regulation of extracellular glutamate levels and synaptic signaling [14, 15].

Other names

System xc- TransporterxCTCystine-glutamate transporterCCBR1System xc-Cystine/glutamate antiporterAmino acid transport system yc+

The primary mechanism of action for drugs targeting this molecule involves the inhibition of the SLC7A11 subunit, which blocks the uptake of extracellular cystine; this depletion leads to a deficiency in intracellular glutathione (GSH), resulting in the lethal accumulation of iron-dependent lipid peroxides and the induction of ferroptosis.