Chang Yu-Chiuan, Wu Jhen-Wei, Wang Chueh-Wen, Jang Anna C-C
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan.
Front Mol Biosci. 2020 Jan 31;6:157. doi: 10.3389/fmolb.2019.00157. eCollection 2019.
The evolutionarily conserved Hippo kinase signaling cascade governs cell proliferation, tissue differentiation and organ size, and can promote tumor growth and cancer metastasis when dysregulated. Unlike conventional signaling pathways driven by ligand-receptor binding to initiate downstream cascades, core Hippo kinases are activated not only by biochemical cues but also by mechanical ones generated from altered cell shape, cell polarity, cell-cell junctions or cell-extracellular matrix adhesion. In this review, we focus on recent advances showing how mechanical force acts through the actin cytoskeleton to regulate the Hippo pathway during cell movement and cancer invasion. We also discuss how this force affects YAP-dependent tissue growth and cell proliferation, and how disruption of that homeostatic relationship contributes to cancer metastasis.
进化上保守的Hippo激酶信号级联控制细胞增殖、组织分化和器官大小，失调时可促进肿瘤生长和癌症转移。与由配体-受体结合驱动以启动下游级联反应的传统信号通路不同，核心Hippo激酶不仅由生化信号激活，还由细胞形状改变、细胞极性、细胞-细胞连接或细胞-细胞外基质黏附产生的机械信号激活。在本综述中，我们重点关注近期的进展，这些进展展示了机械力如何通过肌动蛋白细胞骨架在细胞运动和癌症侵袭过程中调节Hippo通路。我们还讨论了这种力如何影响YAP依赖的组织生长和细胞增殖，以及这种稳态关系的破坏如何导致癌症转移。
