SLC7A11/xCT in cancer: biological functions and therapeutic implications

Amino acid transporters mediate substrates across cellular membranes and their fine-tuned regulations are critical to cellular metabolism, growth, and death. As the functional component of system Xc-, which imports extracellular cystine with intracellular glutamate release at a ratio of 1:1, SLC7A11 has diverse functional roles in regulating many pathophysiological processes such as cellular redox homeostasis, ferroptosis, and drug resistance in cancer. Notably, accumulated evidence demonstrated that SLC7A11 is overexpressed in many types of cancers and is associated with patients' poor prognosis. As a result, SLC7A11 becomes a new potential target for cancer therapy. In this review, we first briefly introduce the structure and function of SLC7A11, then discuss its pathological role in cancer. We next summarize current available data of how SLC7A11 is subjected to fine regulations at multiple levels. We further describe the potential inhibitors of the SLC7A11 and their roles in human cancer cells. Finally, we propose novel insights for future perspectives on the modulation of SLC7A11, as well as possible targeted strategies for SLC7A11-based anti-cancer therapies.