磷酸酯酶D在肿瘤发生发展中的作用研究进展

Advances in studies on phospholipase D in oncogenesis and development

磷酸酯酶D(PLD)作为一种调控机体磷脂代谢的水解酶,其水解产物磷脂酸和二酰基甘油均为细胞内重要的第二信使,参与多种细胞生理功能。PLD在胃癌、结直肠癌、食管癌、肺癌、甲状腺癌和乳腺癌等多种恶性肿瘤中均高表达,通过肿瘤相关信号通路促进细胞癌变和增殖、促进肿瘤细胞浸润和迁移、加速上皮间充质转化和微血管生成及增强免疫逃逸等进程,而靶向诱导PLD蛋白功能缺失可逆转上述进程。PLD在肿瘤发生发展中的作用机制以及PLD抑制剂的研究目前已成为国内外的研究热点。本文从原位肿瘤发生发展、肿瘤侵袭过程、血管生成和肿瘤细胞微环境等方面综述PLD对肿瘤进展的作用,为靶向PLD治疗肿瘤提供临床依据。

Phospholipase D(PLD)is regarded as a lipid-modifying enzyme that regulates phospho⁃lipid metabolism in the body,and its hydrolysis products,phosphatidic acid and diacylglycerol,are both important intracellular second messengers that are involved in a variety of cellular physiological func⁃tions.PLD overexpression is reported in a wide range of cancers such as gastric,colorectal,esopha⁃gus,lung,thyroid and breast cancers.By linking to tumor-associated signaling pathways,PLD overex⁃pression promotes a series of processes such as tumor transformation and proliferation,enhances infil⁃tration and migration,accelerates the occurrence of epithelial-mesenchymal transition and microangio⁃genesis,and stimulates immune escape.However,these process can be reversed by targeting and inducing the loss of function of PLD protein.Currently,the mechanism of PLD in tumor progression and the research on inhibitors targeting PLD have been a hotspot globally.This review outlines the mechanisms of PLD for intracellular regulation including its role in situ tumor development,tumor invasion,tumor angiogenesis,and tumor microenvironments in order to provide more clinical refer⁃ence for the treatment of various tumors by targeting PLD.