Cystine‐glutamate antiporter xCT as a therapeutic target for cancer

Abstract

Cystine/glutamic acid reverse transporter (System Xc−), a member of the amino acid transporter family, consists of two subunits, light chain xCT and heavy chain 4F2hc. xCT is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11), which promotes cystine uptake and glutathione biosynthetic, thus protecting against oxidative stress and ferroptosis. Studies have confirmed that xCT is highly expressed in a variety of tumour and is associated with tumour proliferation, invasion, metastasis, drug resistance and ferroptosis, and can be used as a potential target for tumour treatment. This review provides insights into the biological effects of xCT and contribute to the development of new xCT‐based strategies.

The roles of ferroptosis regulatory gene SLC7A11 in renal cell carcinoma: A multi‐omics study

“…8 Solute carrier family 7 member 11 (SLC7A11) constitutes the major component of the xCT system and is capable of inhibiting ferroptosis by promoting cystine uptake. 8 Accumulating evidence has shown that SLC7A11 is overexpressed in multiple cancers and can promote tumor progression by retarding ferroptosis, leading to metabolic reprogramming. 9 Therefore, SLC7A11 shows great potential as a new target for cancer therapy.…”

Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects

“…System x c − is a cystine/glutamate antiporter with xCT (Slc7a11) as specific subunit and is located mainly in the central nervous system and peripheral organs related to the immune system. xCT expression is enhanced in conditions of increased oxidative stress and/or inflammation, and inhibition of system x c − has been proposed as a treatment strategy for several neurological disorders as well as for diverse cancer types ( Lewerenz et al, 2013 ; Massie et al, 2015 ; Koppula et al, 2018 ; Liu et al, 2020 ). However, despite many attempts, till now none of the available inhibitors are selectively targeting system x c − .…”

Antioxidative Stress: Inhibiting Reactive Oxygen Species Production as a Cause of Radioresistance and Chemoresistance

“…Besides the enzymes that control the glutamine metabolism directly, a cystine/glutamate exchange transporter called system X also plays a critical role in intracellular GSH biosynthesis [ 84 ]. The expression of the light chain of system X is promoted by Nrf2 under the stimulation of oxidative stress, which is closely related to radio- and chemoresistance in tumour cells [ 85 , 86 ]. In Nrf2 knockdown cells, glutathione metabolism is affected [ 80 ], showing the pivotal role of Nrf2 in glutathione metabolism.…”