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

The Solute carrier family 7 member 11 (xCT) is the catalytic subunit of the heterodimeric amino acid transport system xc-, which functions as a sodium-independent cystine/glutamate antiporter [1]. It facilitates the stoichiometric exchange of extracellular cystine for intracellular glutamate, providing the essential precursor for glutathione (GSH) synthesis [2]. By maintaining high intracellular GSH levels, xCT serves as a master regulator of cellular redox homeostasis and a critical defense mechanism against ferroptosis, an iron-dependent form of oxidative cell death [3]. In the context of oncology, many aggressive tumors upregulate xCT to mitigate metabolic oxidative stress, which has led to its investigation as a target for ferroptosis-inducing therapies [4]. Beyond cancer, xCT is involved in neurological disorders because its glutamate export activity can influence synaptic signaling and contribute to excitotoxicity if dysregulated [5]. Pharmacological inhibition of xCT, using agents like sulfasalazine or erastin, aims to deplete cellular antioxidants and sensitize resistant cells to oxidative damage [6]. This inhibition triggers a cascade of lipid peroxidation that ultimately leads to cell death, making it a promising strategy for treating therapy-resistant cancers [7].

Other names

SLC7A11Cystine/glutamate transporterSystem xc- subunit xCTCCBR1Amino acid transport system xc-

Inhibition of the cystine/glutamate antiporter activity leads to the depletion of intracellular cysteine and glutathione, resulting in lethal accumulation of lipid hydroperoxides and induction of ferroptosis [3, 6].