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转录因子FOXOs家族调控肿瘤生物学功能的研究进展

张仙宏, 魏萌萌, 袁冬冬, 吴巍, 李乐^*

宁夏大学生命科学学院，西部特色生物资源保护与利用教育部重点实验室，银川 750021

摘要

叉头框O蛋白(Forkhead box class O proteins, FOXOs)家族是进化较为保守的蛋白质转录因子家族，由FOXO1、FOXO3、FOXO4和FOXO6四个成员组成。FOXOs蛋白家族是一种普遍表达的转录因子，参与调节肿瘤细胞的增殖、凋亡、迁移和氧化应激等诸多生物学活动。而FOXOs的自身活性受翻译后修饰调控，其失活主要是由于其上游的修饰酶过度激活，这为从药物上恢复其活性提供了可能性。值得注意的是，FOXOs在人类肿瘤的发生和发展中不但具有抑制作用，还具有促进作用。本文将对FOXOs的结构及活性调节进行概述，对其抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡的肿瘤抑制作用，参与氧化应激反应维持细胞稳态，以及促进转移、诱导治疗耐药性的肿瘤促进作用进行总结，以期为相关疾病的病理研究提供新的思路，进而开辟新途径，促进更广泛的预防与治疗策略产生。

关键词： FOXOs; 肿瘤; 细胞凋亡; 细胞自噬; 代谢

Research progress on the role of FOXOs family in cancer 

ZHANG Xian-Hong, WEI Meng-Meng, YUAN Dong-Dong, WU Wei, LI Le^*

Key Laboratory of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, School of Life Sciences, Ningxia University, Yinchuan 750021, China

Abstract

The Forkhead box class O proteins (FOXOs) family consists of highly conserved transcription factors, including FOXO1, FOXO3, FOXO4 and FOXO6. Each member of the FOXOs family is ubiquitously expressed and involved in regulating many biological activities such as tumor cell proliferation, apoptosis, migration and oxidative stress. The activity of FOXOs is mainly regulated by post-translational modification, and its inactivation is mainly mediated by the over-activation of its upstream modifying enzymes, which provides a possibility to use drugs to recover its activity. It is worth noting that FOXOs can not only inhibit, but also promote the occurrence and development of human tumors due to the complex effects of FOXOs. This review will summarize the structure and activity regulation of FOXOs, and discuss their tumor inhibiting effects by limiting cell proliferation and inducing apoptosis, as well as their tumor promoting effects by maintaining cell homeostasis, promoting metastasis and inducing drug resistance, so as to provide new ideas for the pathological research of related diseases and open up new ways to promote broader prevention and treatment strategies.

Key words: FOXOs; tumor; apoptosis; autophagy; metabolism

收稿日期：　　录用日期：

通讯作者：李乐　　E-mail: leli@nxu.edu.cn

DOI: 10.13294/j.aps.2022.0053

引用本文：

张仙宏, 魏萌萌, 袁冬冬, 吴巍, 李乐. 转录因子FOXOs家族调控肿瘤生物学功能的研究进展[J]. 生理学报 2022; 74 (5): 843-855.

ZHANG Xian-Hong, WEI Meng-Meng, YUAN Dong-Dong, WU Wei, LI Le. Research progress on the role of FOXOs family in cancer . Acta Physiol Sin 2022; 74 (5): 843-855 (in Chinese with English abstract).