缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制

摘要

肾癌是一种常见的泌尿系统肿瘤,但在临床上对转移性肾癌的治疗手段还非常有限.缺氧是实体肿瘤微环境的一个重要的基本特征.近年来基于分子机制和临床研究的数据表明,低氧诱导因子(hypoxia-inducible factors, HIFs)在肾细胞癌(renal cell carcinoma, RCC)的发生发展中发挥着至关重要的作用.HIF是一类介导细胞适应低氧状况必需的转录激活因子,由α亚基和β亚基组成.研究已经证实,在RCC中HIF-1α和HIF-2α具有相反的作用,前者作为肿瘤抑制因子,而后者作为癌基因发挥功能.本文综述了HIF信号通路在RCC发生发展中的作用及其分子机制,并对靶向HIF信号通路治疗RCC的进行了探讨,以期指导临床肾细胞癌的精准化治疗和进一步的研究.%Renal cancer is a common urologic malignancy. However, the therapeutic options for metastatic renal cancer patients are limited. Hypoxia (low oxygen) is a fundamental microenvironmental determinant of solid tumor pathophysiol-ogy. Recent data from molecular and clinical studies indicate that hypoxia-inducible factors (HIFs) play critical roles in the development and progress of renal cell carcinoma (RCC). The HIF transcription factor family is a type of heterodimeric transcription factor consisting of HIF-α and HIF-β subunits and can transcriptionally activate genes that mediate the hypox-ic response. In RCC, HIF-1α and HIF-2α have opposing effects: HIF-1α is a tumor suppressor while HIF-2α acts as an on-cogene. In this review, we summarize the current advances in understanding the roles and molecular mechanisms of HIF signaling in RCC. We also discuss recent HIF-targeted strategies proposed to improve RCC treatment, which may provide a foundation for further research, including the development of precision medicine for the treatment of RCC.