Post-translational acylation of proteins in colorectal cancer.

Abstract

Accumulating preclinical evidence indicates that protein acylation, a functionally diverse class of post-translational modifications, is implicated in the regulation of protein stability, enzymatic activity, subcellular localization, molecular interactions, and gene transcription. In colorectal cancer (CRC), this modification family has been linked to proliferation, invasion, metastasis, metabolic reprogramming, therapeutic resistance, and immune escape. This review critically summarizes recent advances in five major acylation types associated with CRC: crotonylation, succinylation, lactylation, acetylation, and palmitoylation. We distinguish histone-mediated transcriptional regulation from the direct functional effects of non-histone acylation, and evaluate the mechanistic evidence linking specific modification sites and regulatory enzymes to CRC phenotypes. We also discuss crosstalk between acylation and other post-translational modifications, current detection strategies, and the proposed translational potential of acylation-associated molecules as biomarkers or therapeutic targets. Most available supporting evidence is derived from cell lines and animal models, whereas validation in patient-derived organoids, independent clinical cohorts, and prospective studies remains incompletely characterized. Establishing causality and defining the clinical relevance of protein acylation in CRC will require further studies integrating site-specific mutagenesis, enzyme perturbation, orthogonal detection methods, and physiologically relevant models. Collectively, the reviewed body of work frames protein acylation as a biologically relevant regulatory axis in CRC, while underscoring that additional rigorous investigation is needed to realize its translational potential.