HIF-1α和ARNT在肿瘤转移及耐药中作用的研究进展

Research progress of HIF-1αand ARNT in tumor metastasis and drug resistance

缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是组织和细胞发生低氧应激反应的重要标志物。HIF-1是由HIF-1α和芳香烃受体核转位蛋白(aryl hydrocarbon receptor nuclear translocator,ARNT)亚基组成的异源二聚体转录因子。HIF-1α和ARNT主要有两种活化途径,除了氧依赖途径外,细胞因子和生长因子等在常氧条件下也可以通过与其相应受体结合的方式使其活化,二者在肿瘤的发生,发展,转移和耐药过程中发挥重要的调控作用。现就HIF-1α和ARNT的活化方式以及在肿瘤转移和耐药的作用等方面进行综述,继而为肿瘤的发生机制和治疗提供新思路。

Hypoxia inducible factor-1(HIF-1)is an important marker of hypoxia stress in tissues and cells.HIF-1 is a heterodimeric transcription factor composed of HIF-1alpha and aryl hydrocarbon receptor nuclear translocator(ARNT)subunits.HIF-1αand ARNT play important regulatory roles in tumorigenesis,development,metastasis and drug resistance.The mechanisms which activate HIF are receptor-mediated signal pathways and the hypoxic signal pathways.Here we review the activation of HIF-1αand ARNT,as well as the role of tumor metastasis and drug resistance.