《生命科学》 2021, 33(7): 810-816

靶向内质网应激作为肿瘤治疗的新策略

刘要甫^1,2 , 谭正之¹ , 田　芳³ , 杨义力^1,2,4,*

¹中国医学科学院苏州系统医学研究所，苏州 215123 ²北京协和医学院，北京 100730 ³郑州大学基础医学院病理生理学系，郑州 450001 ⁴国际遗传工程和生物技术中心中国区域研究中心，泰州 225326

摘　要：

内质网应激是细胞应对蛋白质突变和表达水平异常的防御性反应，包括未折叠蛋白反应(UPR)、内质网相关蛋白质降解(ERAD) 和自噬体形成等多个组成部分。许多研究指出，肿瘤细胞依赖高水平的内质网应激反应以维持生存和高速生长，干扰UPR 和ERAD 可抑制肿瘤细胞的生长。同时，癌细胞发生抗
药的关键机制是产生新的突变，这些突变可能会进一步诱导UPR 和ERAD 等，使抗药癌细胞对内质网应激的抑制剂更加敏感。因此，面对后基因组时代发现的肿瘤细胞突变的多样性、异质性和持续性，靶向细胞对突变的反应——内质网应激，是值得关注和研究的新抗肿瘤策略。

通讯作者：杨义力 , Email:yili.yang@icgeb.cn

Targeting endoplasmic reticulum stress as a novel strategy for cancer treatment

LIU Yao-Fu^1,2 , TAN Zheng-Zhi¹ , TIAN Fang³ , YANG Yi-Li^1,2,4,*

¹Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou 215123, China ²Peking Union Medical College, Beijing 100730, China ³Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China ⁴International Centre of Genetic Engineering and Biotechnology, China Regional Research Centre, Taizhou 225326, China

Abstract:

Endoplasmic reticulum stress is a cellular defense response to mutated or inadequately expressed proteins. It is composed of multiple components, including unfolded protein response (UPR), endoplasmic reticulum-associated degradation (ERAD), and autophagy formation. It has been revealed that tumor cells rely on high level of ER stress response to survive and grow rapidly. It has also been shown that meddling UPR and ERAD often induces inhibition of tumor cell growth. Of note, novel mutations are largely responsible for tumor cells to become resistant to chemotherapeutics. It is conceivable that these mutations are able to further augment ER stress response and make the cells more susceptible to inhibition of ER stress response. With the increasing understanding of cancer mutations, their diversity, heterogeneity, and continuity, we believe that targeting the cellular response to mutations represents a novel anti-tumor strategy that is worthy of being further studied and explored.

Communication Author：YANG Yi-Li , Email:yili.yang@icgeb.cn