摘要
泛素激酶PINK1是线粒体质量控制中重要的激酶,在癌症发生发展中通常呈双重调控作用,其促癌或抑癌作用与肿瘤类型、微环境及细胞代谢状态相关。研究表明PINK1的表达在不同肿瘤细胞中呈异质性,并且PINK1还可通过调节代谢关键酶的活性调控代谢重编程。本文主要总结转录因子NF-κB和p53以及翻译后修饰包括乙酰化、泛素化和磷酸化对PINK1表达调控的分子机制。PINK1通过调控线粒体自噬、生物发生、动态和代谢介导线粒体质量控制,及其对肿瘤病理生理包括耐药和上皮间质转化的调控作用,以及PINK1在结直肠癌、肝癌和肺癌中作用的研究进展,可为开发精准靶向PINK1的癌症治疗策略提供理论依据。
As a crucial kinase in mitochondrial quality control,the ubiquitin kinase PINK1 exhibits a dual regulato-ry role in tumorigenesis and progression.Its oncogenic or tumor-suppressive effects are associated with tumor type,micro-environment,and cellular metabolic status.Studies have demonstrated that the expression of PINK1 is heterogeneous across different tumor cells.Additionally,PINK1 can regulate metabolic reprogramming by modulating the activity of key metabol-ic enzymes.This review will summarize the molecular mechanisms by which transcription factors NF-κB and p53,along with post-translational modifications(acetylation,ubiquitination,and phosphorylation),regulate PINK1 expression.It will also discuss how PINK1 mediates mitochondrial quality control via regulating mitophagy,biogenesis,dynamics,and metab-olism,as well as its regulatory roles in tumor pathophysiology(including drug resistance and epithelial-mesenchymal tran-sition).Additionally,research progress on PINK1's functions in colorectal,liver,and lung cancers will be covered,provi-ding a theoretical basis for developing precise PINK1-targeted cancer therapies.
作者
王晨懿
王晨希
邹宇
WANG Chen-yi;WANG Chen-xi;ZOU Yu(Department of Histology and Embryology,College of Basic Medical Sciences,China Medical University,Shenyang 110122,China;First Clinical School,China Medical University,Shenyang 110122,China;Fourth Clinical School,China Medical University,Shenyang 110122,China)
出处
《解剖科学进展》
2025年第6期884-886,888,共4页
Progress of Anatomical Sciences
基金
国家自然科学基金(82102740)。
