Cysteine Metabolism in the Control of Oxidative Stress in Cancer, Focusing on Carbon and Sulfur Metabolism.

Cysteine is a critical metabolic hub in cancer cells, essential for survival and progression, as it serves as a precursor to glutathione, a key antioxidant that mitigates oxidative stress and contributes to chemoresistance. Beyond antioxidation, cysteine metabolism supports cancer growth by generating metabolic intermediates such as pyruvate and hydrogen sulfide (H2S), which facilitate energy production and signaling. Its synthesis is tightly integrated with one-carbon metabolism involving methionine and serine, pathways vital for methylation and epigenetic regulation. Cysteine also modulates other metabolic pathways, such as the glucose-dependent ones, helping maintain cellular energy and redox balance under stress. The degradation of cysteine produces H2S, a gasotransmitter, which regulates antioxidant defenses through the scavenging of reactive oxygen species (ROS) and the activation of the Keap1/Nrf2 pathway. H2S further promotes mitochondrial function, metabolic reprogramming, glycolysis, and angiogenesis, all of which contribute to tumor growth and survival. Therapeutic strategies targeting cysteine availability and H2S production hold promise but must consider the capacity of cancer cells for endogenous cysteine synthesis, which is yet to be explored. Overall, the multifaceted roles of cysteine metabolism underscore its importance in cancer bioenergetics, redox homeostasis, and resistance mechanisms, presenting valuable avenues for intervention.