乙酰辅酶A代谢与肿瘤转移

Acetyl-CoA metabolism and cancer metastasis

转移是恶性肿瘤最重要的特征之一,也是肿瘤患者最主要的致死原因。肿瘤转移涉及肿瘤细胞自身、肿瘤与微环境间的相互作用等多方面调控因素。然而,肿瘤转移的具体调控机制还远未揭示清楚。代谢重编程是肿瘤的另一重要特征,在肿瘤发生、发展中发挥重要作用。乙酰辅酶A是细胞内关键的代谢中间物,在蛋白乙酰化和脂质合成代谢中起关键作用。已知肿瘤发生发展过程中乙酰辅酶A代谢发生了重编程,为肿瘤的快速生长提供了合成代谢原料。近年来,多项研究在不同类型的肿瘤中发现了乙酰辅酶A代谢与肿瘤转移表型存在密切关联,并进一步揭示了乙酰辅酶A代谢调控肿瘤转移的作用机制。本文将从以下三方面对乙酰辅酶A代谢调控及其在肿瘤转移中的作用及机制进行综述:(1)概述乙酰辅酶A的功能、主要代谢途径及关键代谢酶;(2)乙酰辅酶A代谢重编程通过调控肿瘤细胞上皮-间质转化、黏附迁移能力以及干性等机制影响肿瘤的侵袭转移;(3)乙酰辅酶A代谢重编程调控肿瘤转移研究展望。

Metastasis is an important hallmark of cancer and accounts for the majority of cancer-associated death.Cancer metastasis is regulated by multi-factors such as cancer cell itself and interactions between cancer cells and microenvironment.However,metastasis remains the most poorly understood component in cancer pathogenesis.Metabolic reprogramming is another important feature of cancer.Acetyl-CoA is a central metabolic intermediate,and plays a vital role in protein acetylation and lipid synthesis.Previous studies have shown that Acetyl-CoA metabolic alternation occurs in cancer progression,providing anabolic materials for the rapid proliferation of cancer cells.In recent years,several studies have reported close correlations between AcetylCoA metabolism alterations and tumor metastasis in several types of cancers,and have revealed the mechanisms underlying how Acetyl-CoA metabolic alterations promote cancer metastasis.This review will summarize recent progresses on the role Acetyl-CoA metabolic alteration in cancer metastasis from the following aspects:(1) brief introduction of the main metabolic pathways,key metabolic enzymes,and physiological roles of Acetyl-CoA metabolism;(2) Acetyl-CoA metabolism alterations regulate cancer metastasis by inducing epithelial-mesenchymal transition,cell adhesion and migration,and sternness of cancer cells;(3) future directions for the researches on the roles of Acetyl-CoA metabolism reprogramming in cancer metastasis.