The Roles of Protein S-Palmitoylation in Cancers: From Dynamic Modulation to Therapeutic Potential

Protein S-palmitoylation is a highly conserved posttranslational lipid modification that occurs on cysteine residues and critically influences protein maturation, subcellular localization, trafficking, and stability. Owing to its unique reversibility and dynamic nature, S-palmitoylation plays a pivotal role in cancer. This review comprehensively summarized the expression profiles and distribution of key cancer-related S-palmitoylation enzymes in recent years. Importantly, we highlight the specific mechanisms by which the dual states of palmitoylation and depalmitoylation function as a dynamic regulatory axis during the transformation of cancer cells into cancer stem cells and during the transition from a normal tissue environment to a tumor microenvironment. Furthermore, we discussed emerging therapeutic strategies targeting S-palmitoylation, including the development of specific inhibitors and competitive blockade of substrate-binding sites, which offer additional insights into the translational potential of S-palmitoylation as a therapeutic target for cancer.