The role of succinylation-mediated metabolic reprogramming in tumor progression.

Metabolic reprogramming is a hallmark of tumors, whereby cancer cells remodel their own metabolism to meet the biosynthetic, energetic, and signaling demands required for rapid proliferation and malignant transformation. Posttranslational modifications (PTMs) serve as dynamic molecular switches that fine-tune cellular metabolic networks by precisely modulating the activity, stability, and subcellular localization of metabolic enzymes. This regulatory plasticity drives context-dependent metabolic reprogramming in tumor cells, enabling them to adapt to fluctuating physiological demands or pathological stressors while establishing tumor-specific metabolic signatures critical for survival and progression. Among PTMs, lysine succinylation-a recently identified modification catalyzed by succinyl-CoA-has emerged as a critical regulator of cancer metabolism. This unique modification involves the transfer of a negatively charged four-carbon succinyl group to lysine residues, inducing conformational and functional changes in target proteins. Notably, succinylation is evolutionarily conserved across eukaryotes and prokaryotes and has a broad influence on central metabolic pathways, including the tricarboxylic acid (TCA) cycle, amino acid metabolism, and lipid homeostasis. Mounting evidence highlights its dual roles in both sustaining tumorigenic metabolism and directly activating oncogenic signaling cascades. This review summarizes current insights into how succinylation rewires tumor metabolism and delineates its mechanistic contributions to cancer progression.