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Role of post-translational modifications in cancer metabolic reprogramming
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DOI：10.1016/j.gendis.2026.102372.png)
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Abstract
En 中文
Post-translational modifications (PTMs) are enzymatic or chemical processes that dynamically regulate protein function by covalently attaching or removing specific chemical groups to amino acid residues. These modifications include classical types such as phosphorylation, ubiquitination, and acetylation. Due to the rapid advancement of proteomics and mass spectrometry technologies, novel acylation modifications, including succinylation, lactylation, crotonylation, and palmitoylation, have garnered attention in various research fields. These modifications are prevalent on key proteins, such as metabolic enzymes and histones, playing essential roles in processes such as energy metabolism, gene transcription, and signal transduction regulation. In oncology, metabolic reprogramming represents a hallmark of cancer progression, characterized by dysregulation in glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism. PTMs orchestrate cellular metabolism through multifaceted mechanisms, including direct modulation of metabolic enzyme activity, alteration of metabolite flux, and rewiring of signaling networks. For instance, Ub ligase (E3) ubiquitin ligases selectively degrade rate-limiting metabolic enzymes via the ubiquitin‒proteasome system, thereby redirecting metabolic pathways. Notably, lactate serves not only as an energy substrate fueling the oncogenic Warburg effect but also as a metabolic precursor promoting histone lactylation modifications, which epigenetically reprogram oncogene expression. Current challenges in targeting PTMs include inadequate mechanistic understanding of emerging modifications, identification of cell-specific druggable targets, and complex crosstalk within PTM networks. This review uniquely dissects the bidirectional regulatory axis between PTMs, particularly acylation modifications, and tumor metabolic networks, providing novel therapeutic perspectives for clinical intervention.
Keywords:
Cancer
Epigenetics
Metabolic reprogramming
Post-translational modifications
Targeted therapy
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