Xiao Yi, Dong Jixin
Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cancers (Basel). 2021 Dec 10;13(24):6214. doi: 10.3390/cancers13246214.
Cell cycle progression is an elaborate process that requires stringent control for normal cellular function. Defects in cell cycle control, however, contribute to genomic instability and have become a characteristic phenomenon in cancers. Over the years, advancement in the understanding of disrupted cell cycle regulation in tumors has led to the development of powerful anti-cancer drugs. Therefore, an in-depth exploration of cell cycle dysregulation in cancers could provide therapeutic avenues for cancer treatment. The Hippo pathway is an evolutionarily conserved regulator network that controls organ size, and its dysregulation is implicated in various types of cancers. Although the role of the Hippo pathway in oncogenesis has been widely investigated, its role in cell cycle regulation has not been comprehensively scrutinized. Here, we specifically focus on delineating the involvement of the Hippo pathway in cell cycle regulation. To that end, we first compare the structural as well as functional conservation of the core Hippo pathway in yeasts, flies, and mammals. Then, we detail the multi-faceted aspects in which the core components of the mammalian Hippo pathway and their regulators affect the cell cycle, particularly with regard to the regulation of E2F activity, the G1 tetraploidy checkpoint, DNA synthesis, DNA damage checkpoint, centrosome dynamics, and mitosis. Finally, we briefly discuss how a collective understanding of cell cycle regulation and the Hippo pathway could be weaponized in combating cancer.
细胞周期进程是一个复杂的过程，需要严格控制以实现正常的细胞功能。然而，细胞周期控制中的缺陷会导致基因组不稳定，并已成为癌症的一个特征性现象。多年来，对肿瘤中细胞周期调控紊乱的认识不断进步，推动了强效抗癌药物的研发。因此，深入探究癌症中的细胞周期失调可为癌症治疗提供治疗途径。Hippo信号通路是一个在进化上保守的调控网络，控制器官大小，其失调与多种类型的癌症有关。尽管Hippo信号通路在肿瘤发生中的作用已得到广泛研究，但其在细胞周期调控中的作用尚未得到全面审视。在这里，我们特别关注描绘Hippo信号通路在细胞周期调控中的作用。为此，我们首先比较酵母、果蝇和哺乳动物中核心Hippo信号通路的结构和功能保守性。然后，我们详细阐述哺乳动物Hippo信号通路的核心成分及其调节因子影响细胞周期的多方面情况，特别是在E2F活性调节、G1四倍体检查点、DNA合成、DNA损伤检查点、中心体动力学和有丝分裂方面。最后，我们简要讨论如何将对细胞周期调控和Hippo信号通路的综合理解应用于抗癌斗争。
