SLC7A11 as a bridge between ferroptosis and disulfidptosis: a promising target for tumor treatment
Hui Qiu, Jing Liu, Nan Shao, Juanjuan Zhao, Chao Chen, Yuanye Jiang, Xu Zhao, Lin Xu
Abstract
Cell death is a basic physiological process involved in embryonic development, aging, immune responses and other life processes. In particular, ferroptosis and disulfidptosis are two forms of regulatory cell death (RCD) that have been identified in recent years as being caused by imbalances in cellular metabolism. Solute Carrier Family 7 Member 11 (SLC7A11, xCT), a cystine transporter, is often highly expressed in tumor cells, which not only participates in the synthesis of glutathione (GSH), but also plays an indispensable role in the inhibition of oxidative stress-induced ferroptosis. However, glucose starvation of SLC7A11 high tumor cells consumes a large amount of NADPH, leading to disulfide stress in actin cytoskeletal proteins, which triggers disulfidptosis. These findings suggest that there is an intrinsic relationship between ferroptosis and disulfidptosis and that SLC7A11 connects the regulation of both forms of death. In this article, we first reviewed the regulatory mechanism controlling SLC7A11 expression and its function and then focused on its role and mechanism in mediating ferroptosis and disulfidptosis in tumorigenesis and treatment. Finally, we carefully discussed the intrinsic links between ferroptosis and disulfidptosis as well as the remaining scientific issues related to their mediation of tumorigenesis and treatment, aiming to provide a new perspective for cancer treatment, especially in the development of strategies for targeted treatment against specific metabolic pathways. • SLC7A11, a multipass transmembrane protein, mediates the cystine/glutamate antiporter activity in the system xc− and is overexpressed in multiple human cancers. • SLC7A11 has two distinct functions in ferroptosis and disulfidptosis, suggesting a possible intrinsic link between these two types of cell death. • SLC7A11 plays a vital role in the occurrence and development of tumors, and is emerging as a promising target in oncotherapy.