遗传 ›› 2018, Vol. 40 ›› Issue (5): 341-356.doi: 10.16288/j.yczz.17-406

• 综述 •    下一篇

缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制

邹俊遐1,陈科2()   

  1. 1. 华中科技大学同济医学院附属同济医院儿科,武汉 430030
    2. 华中科技大学同济医学院附属同济医院泌尿外科,武汉 430030
  • 收稿日期:2017-12-11 修回日期:2018-01-13 出版日期:2018-05-20 发布日期:2018-03-30
  • 通讯作者: 陈科 E-mail:kechen@hust.edu.cn
  • 作者简介:邹俊遐,本科,护师,研究方向:儿童护理和肿瘤疾病专科护理。E-mail: 459382103@qq.com
  • 基金资助:
    国家自然科学基金(81402105);国家自然科学基金(81772721)

Roles and molecular mechanisms of hypoxia-inducible factors in renal cell carcinoma

Zou Junxia1,Chen Ke2()   

  1. 1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    2. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • Received:2017-12-11 Revised:2018-01-13 Online:2018-05-20 Published:2018-03-30
  • Contact: Chen Ke E-mail:kechen@hust.edu.cn
  • Supported by:
    Supported by National Natural Science Foundation of China(81402105);Supported by National Natural Science Foundation of China(81772721)

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。

关键词: 缺氧, 低氧诱导因子(HIFs), 肾细胞癌, VHL

Abstract:

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 pathophysiology. 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 hypoxic response. In RCC, HIF-1α and HIF-2α have opposing effects: HIF-1α is a tumor suppressor while HIF-2α acts as an oncogene. 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.

Key words: hypoxia, hypoxia-inducible transcription factors (HIFs), renal cell carcinoma, von Hippel-Lindau (VHL)