缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制

doi:10.16288/j.yczz.17-406

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. 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

Junxia Zou¹,Ke Chen²()

^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/Abstract

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)

邹俊遐, 陈科. 缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制[J]. 遗传, 2018, 40(5): 341-356.

Junxia Zou, Ke Chen. Roles and molecular mechanisms of hypoxia-inducible factors in renal cell carcinoma[J]. Hereditas(Beijing), 2018, 40(5): 341-356.

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缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制

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

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