Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Semin Cancer Biol. 2018 Jun;50:101-114. doi: 10.1016/j.semcancer.2017.11.007. Epub 2017 Nov 16.
The Forkhead box O (FoxO) proteins comprise a family of evolutionarily conserved transcription factors that predominantly function as tumor suppressors. These proteins assume diverse roles in the cellular anti-neoplastic response, including regulation of apoptosis and autophagy, cancer metabolism, cell-cycle arrest, oxidative stress and the DNA damage response. More recently, FoxO proteins have been implicated in cancer immunity and cancer stem-cell (CSC) homeostasis. Interestingly, in some sporadic sub-populations, FoxO protein function may also be manipulated by factors such as β-catenin whereby they instead can facilitate cancer progression via maintenance of CSC properties or promoting drug resistance or metastasis and invasion. This review highlights the essential biological functions of FoxOs and explores the areas that may be exploited in FoxO protein signaling pathways in the development of novel cancer therapeutic agents.
叉头框 O（FoxO）蛋白家族是一组进化上保守的转录因子，主要作为肿瘤抑制因子发挥作用。这些蛋白在细胞抗肿瘤反应中发挥多种作用，包括调节细胞凋亡和自噬、癌症代谢、细胞周期停滞、氧化应激和 DNA 损伤反应。最近，FoxO 蛋白已被牵连到癌症免疫和癌症干细胞（CSC）稳态中。有趣的是，在一些散发性亚群中，FoxO 蛋白功能也可能受到β-catenin 等因素的操纵，通过维持 CSC 特性或促进耐药性或转移和侵袭，反而促进癌症进展。本综述强调了 FoxOs 的基本生物学功能，并探讨了在 FoxO 蛋白信号通路中可能被利用的领域，以开发新型癌症治疗药物。
