摘要
缺氧诱导因子-1α(HIF-1α)在癌症进展中是一个关键的转录因子,同时也是癌症靶向治疗的一个重要指标.HIF-1α的活性取决于氧气的存在与否.在有氧环境中,HIF-1α被完全失活并通过泛素蛋白酶体途径降解.相反,在缺氧环境中,它进入细胞核积累,随后上调多个与癌症进展相关的基因.HIF-1α在各类肿瘤组织中均高度表达,过表达的HIF-1α及其下游基因通过血管拟态、糖酵解、侵袭迁移、免疫逃逸以及肿瘤耐药性等多种机制支持癌症进展.通过靶向HIF-1α及其下游信号分子可以控制癌症的进展,故调控HIF-1α基因的mRNA和蛋白水平成为抑制癌症的新途径.鉴于HIF-1α以及相关通路调节因子的靶向治疗可能成为多种恶性肿瘤新的治疗手段,本文就HIF-1α在肿瘤生物学功能中的研究进展进行综述.
Abstract
Hypoxia inducible factor-1α(HIF-1α)is a key transcription factor in cancer progression and an important target for cancer-targeted therapy and its activity depends on the presence or absence of oxygen.In an aerobic environment,HIF-1α is completely inactivated and degraded through the ubiquitin-proteasome pathway.On the contrary,in hypoxic environments,HIF-1α accumulates in the nucleus and subsequently upregulates several genes related to cancer progression.HIF-1α is highly expressed in various types of tumor tissues,and its overexpression,along with downstream genes,supports cancer progression through various mechanisms such as vascular mimicry,glycolysis,invasion,migration,immune escape,and tumor drug resistance.Targeting HIF-1α and its downstream signaling molecules can regulate the development and progression of cancer.Therefore,regulating HIF-1 α,mRNA,and protein levels become new pathways for inhibiting cancer.Considering targeted therapy against HIF-1α and related pathway regulatory factors may become a new therapeutic approach for various malignant tumors,so this article reviews the role of HIF-1α in tumor cell biology and the mechanisms of related drugs.
基金项目
国家自然科学基金项目(82160768)
国家自然科学基金项目(82002822)
广西科技厅中央引导地方科技发展资金项目(桂科ZY21195024)
广西研究生教育创新计划项目(YCSW2023408)
NETL
NSTL
万方数据