Wnt/β-catenin通路调控铁死亡在肝癌中的研究进展  

Wnt/β⁃catenin pathway regulates iron death in hepatocellular carcinoma

作　　者：陈锦浩 曹智 陈家诚 郑进方 CHEN Jinhao;CAO Zhi;CHEN Jiacheng;ZHENG Jinfang(Clinical College of Hainan Medical College,Haikou 571199,China;Department of Hepatobiliary and Pancreatic Surgery,Hainan Provincial People's Hospital,Hainan Medical College,Haikou 571199,China)

机构地区：[1]海南医学院临床学院,海南海口571199 [2]海南医学院附属海南医院(海南省人民医院)肝胆胰外科,海南海口570311

出　　处：《海南医学院学报》2024年第14期1104-1110,共7页Journal of Hainan Medical University

基　　金：海南省重点研发计划(ZDYF2020134);海南省重点研发项目(ZDYF2022SHFZ131);海南省临床医学研究中心项目(LCYX202208)。

摘　　要：铁死亡被认为是一种铁依赖性、非凋亡形式的调节性细胞死亡,主要由活性氧产生和铁稳态失衡导致严重脂质过氧化而引发的,它可诱导相关因子可通过不同途径直接或间接影响谷胱甘肽过氧化物酶,导致抗氧化能力下降和细胞中脂质活性氧积累,最终导致氧化细胞死亡。同时,铁死亡受到了多种途径调控,如铁代谢、线粒体活性、氧化还原稳态以及与疾病相关信号通路等。据研究报道,铁死亡代谢途径失调可影响肝癌的发生、发展。目前铁死亡导致疾病的分子机制知之甚少,但铁死亡相关基因和通路与肝癌进展有关。研究发现,Wnt/βcatenin信号通路异常激活与肝癌的复发、侵袭、转移以及免疫逃逸有关,且与铁死亡之间存在密切的联系。该通路可通过调控铁死亡的发生从而进一步加重肝癌的恶化。目前该领域在肝癌中已取得一定的实质性进展。因此,在本综述中通过概述铁死亡的分子机制及其在肝癌中的作用,探讨其影响肝癌进展的过程,同时,具体分析Wnt/βcatenin信号通路调控铁死亡的发生过程,为未来肝癌的治疗提供可靠的科学理论依据。Iron death is considered to be an iron-dependent,non-apoptotic form of regulated cell death,which is mainly trig-gered by reactive oxygen species(ROS)production and imbalance of iron homeostasis leading to severe lipid peroxidation,and it induces related factors that can directly or indirectly affect glutathione peroxidase through different pathways,leading to decreased antioxidant capacity and accumulation of lipid reactive oxygen species(ROS)in the cells,and ultimately leading to oxidative cell death.Meanwhile,iron death is regulated by various pathways,such as iron metabolism,mitochondrial activity,redox homeosta-sis,and disease-related signalling pathways.It has been reported that dysregulation of iron death metabolic pathways can affect the development and progression of hepatocellular carcinoma.Little is known about the molecular mechanisms by which iron death leads to disease,but iron death-related genes and pathways are associated with hepatocellular carcinoma progression.It was found that abnormal activation of the Wnt/β-catenin signalling pathway is associated with recurrence,invasion,metastasis and immune escape of hepatocellular carcinoma,and is closely linked to iron death.This pathway can further aggravate the progression of hepa-tocellular carcinoma by regulating the occurrence of iron death.Some substantial progress has been made in this field in hepatocellu-lar carcinoma.Therefore,in the present review,we will explore the process of iron death by outlining its molecular mechanism and its role in hepatocellular carcinoma,and at the same time,we will specifically analyse the Wnt/β-catenin signaling pathway to regulate the process of iron death,so as to provide a reliable scientific theoretical basis for the treatment of hepatocellular carcino-ma in the future.

关 键 词：Wnt/βcatenin信号通路 铁死亡 肝癌 侵袭 转移 免疫逃逸 

分 类 号：R735.7[医药卫生—肿瘤]