三磷酸腺苷-柠檬酸裂解酶在肿瘤中的研究进展

Research Progress on Roles of Adenosine Triphosphate-Citrate Lyase in Tumors

癌细胞最重要的代谢特征之一是脂肪酸从头合成的增多。脂肪酸是所有生物膜脂的重要组成部分,是能量代谢的重要底物。三磷酸腺苷-柠檬酸裂解酶(adenosine triphosphatecitrate lyase,ACLY)主要存在于细胞质,是糖代谢与脂肪酸从头合成之间的桥梁。ACLY在多数肿瘤细胞中高表达,通过促进脂肪酸从头合成,或者参与不同的调控通路,从而影响肿瘤的发生、转移及耐药等生物学过程。ACLY受到多种基因、转录因子以及翻译后修饰调节,抑制ACLY能够抑制肿瘤细胞的增殖、侵袭、转移。目前越来越多的ACLY抑制剂及其在肿瘤中的应用正在被发掘研究。全文将对ACLY在多种肿瘤中的相关调控机制及其研究现状进行综述。

Fatty acids are main component of cell membrane lipids and important substrates for energy metabolism,the de novo fatty acid synthesis is significantly increased in cancer cells.Adenosine triphosphate-citrate lyase(ACLY)exists mainly in the cytoplasm of cells,acting as a bridge between glucose metabolism and de novo synthesis of fatty acids.Highly expressed in most tumor cells,ACLY affects the occurrence,metastasis,drug resistance and other biological process of tumors by promoting de novo fatty acid synthesis or participating in various regulatory pathways.ACLY is regulated by a variety of genes,transcription factors and post-translational modifications.Inhibition of ACLY can inhibit the proliferation,invasion and metastasis of tumor cells,at present more ACLY inhibitors have been developed and their application in cancer treatment is being explored.In this paper,we will review the research progress on the roles and regulatory mechanism of ACLY in a variety of malignant tumors.