Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, PR China.
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, PR China.
Biomed Pharmacother. 2023 Dec;168:115741. doi: 10.1016/j.biopha.2023.115741. Epub 2023 Oct 19.
Acetyl-coenzyme A (acetyl-CoA), an essential metabolite, not only takes part in numerous intracellular metabolic processes, powers the tricarboxylic acid cycle, serves as a key hub for the biosynthesis of fatty acids and isoprenoids, but also serves as a signaling substrate for acetylation reactions in post-translational modification of proteins, which is crucial for the epigenetic inheritance of cells. Acetyl-CoA links lipid metabolism with histone acetylation to create a more intricate regulatory system that affects the growth, aggressiveness, and drug resistance of malignancies such as glioblastoma, breast cancer, and hepatocellular carcinoma. These fascinating advances in the knowledge of acetyl-CoA metabolism during carcinogenesis and normal physiology have raised interest regarding its modulation in malignancies. In this review, we provide an overview of the regulation and cancer relevance of main metabolic pathways in which acetyl-CoA participates. We also summarize the role of acetyl-CoA in the metabolic reprogramming and stress regulation of cancer cells, as well as medical application of inhibitors targeting its dysregulation in therapeutic intervention of cancers.
乙酰辅酶 A（acetyl-CoA）是一种必需代谢物，不仅参与众多细胞内代谢过程，为三羧酸循环供能，还是脂肪酸和异戊二烯的生物合成的关键枢纽，而且作为蛋白质翻译后修饰中乙酰化反应的信号底物，对于细胞的表观遗传具有重要作用。乙酰辅酶 A 将脂质代谢与组蛋白乙酰化联系起来，形成一个更复杂的调控系统，影响胶质母细胞瘤、乳腺癌和肝癌等恶性肿瘤的生长、侵袭性和耐药性。这些在致癌作用和正常生理过程中乙酰辅酶 A 代谢的知识的令人着迷的进展引起了人们对其在恶性肿瘤中调节的兴趣。在这篇综述中，我们概述了乙酰辅酶 A 参与的主要代谢途径的调控和癌症相关性。我们还总结了乙酰辅酶 A 在癌细胞代谢重编程和应激调节中的作用，以及靶向其失调在癌症治疗干预中的抑制剂的医学应用。
