Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411, Republic of Singapore; Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
Mechanobiology Institute, National University of Singapore, 5A Engineering Drive, 117411, Republic of Singapore.
FEBS Lett. 2014 Aug 19;588(16):2663-70. doi: 10.1016/j.febslet.2014.04.012. Epub 2014 Apr 18.
Organ size is controlled by the concerted action of biochemical and physical processes. Although mechanical forces are known to regulate cell and tissue behavior, as well as organogenesis, the precise molecular events that integrate mechanical and biochemical signals to control these processes are not fully known. The recently delineated Hippo-tumor suppressor network and its two nuclear effectors, YAP and TAZ, shed light on these mechanisms. YAP and TAZ are proto-oncogene proteins that respond to complex physical milieu represented by the rigidity of the extracellular matrix, cell geometry, cell density, cell polarity and the status of the actin cytoskeleton. Here, we review the current knowledge of how YAP and TAZ function as mechanosensors and mechanotransducers. We also suggest that by deciphering the mechanical and biochemical signals controlling YAP/TAZ function, we will gain insights into new strategies for cancer treatment and organ regeneration.
器官大小受生化和物理过程的协同作用控制。尽管机械力已被证实可调节细胞和组织行为以及器官发生,但将机械和生化信号整合以控制这些过程的确切分子事件尚不完全清楚。最近描述的 Hippo-肿瘤抑制网络及其两个核效应物 YAP 和 TAZ,揭示了这些机制。YAP 和 TAZ 是原癌基因蛋白,它们响应细胞外基质的刚性、细胞几何形状、细胞密度、细胞极性和肌动蛋白细胞骨架的状态等复杂物理环境。在这里,我们回顾了 YAP 和 TAZ 作为机械感受器和机械转导器的作用的现有知识。我们还提出,通过破译控制 YAP/TAZ 功能的机械和生化信号,我们将深入了解癌症治疗和器官再生的新策略。