Is palmitoylation a good target for cancer treatment?

Abstract

Protein S-palmitoylation is a reversible post-translational lipid modification process in which fatty acids are added to proteins. This process is enzyme-driven and activated by protein acyltransferases (PATs), which contain a conserved catalytic domain characterised by an aspartate-histidine-histidine-cysteine (DHHC) amino acid sequence motif. S-palmitoylation plays a vital role in the regulation of protein location, trafficking, and function, as well as in signaling pathways, including those in cancer cells. The PAT enzymes involved in mediating palmitoylation have recently been proven to be effective therapeutic targets for cancer treatment. N-Ras, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathways can be defined as therapeutic targets involved in tumour growth and development, all of which are regulated by S-palmitoylation. This critical review aims to investigate whether targeting the enzymes that mediate the S-palmitoylation of N-Ras, PD-1 and PD-L1 represents an effective therapeutic strategy in cancer.