Chakraborty Sayan, Hong Wanjin
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A-STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
Cancers (Basel). 2018 Feb 6;10(2):45. doi: 10.3390/cancers10020045.
In addition to the structural and scaffolding role, the extracellular matrix (ECM) is emerging as a hub for biomechanical signal transduction that is frequently relayed to intracellular sensors to regulate diverse cellular processes. At a macroscopic scale, matrix rigidity confers long-ranging effects contributing towards tissue fibrosis and cancer. The transcriptional co-activators YAP/TAZ, better known as the converging effectors of the Hippo pathway, are widely recognized for their new role as nuclear mechanosensors during organ homeostasis and cancer. Still, how YAP/TAZ senses these "stiffness cues" from the ECM remains enigmatic. Here, we highlight the recent perspectives on the role of agrin in mechanosignaling from the ECM via antagonizing the Hippo pathway to activate YAP/TAZ in the contexts of cancer, neuromuscular junctions, and cardiac regeneration.
除了其结构和支架作用外,细胞外基质(ECM)正逐渐成为生物力学信号转导的枢纽,这些信号常常传递给细胞内传感器以调节各种细胞过程。在宏观尺度上,基质硬度具有远距离效应,促进组织纤维化和癌症发展。转录共激活因子YAP/TAZ,更广为人知的是作为Hippo通路的汇聚效应器,因其在器官稳态和癌症期间作为核机械传感器的新作用而被广泛认可。然而,YAP/TAZ如何感知来自ECM的这些“硬度信号”仍然是个谜。在这里,我们重点介绍了最近关于聚集蛋白在通过拮抗Hippo通路从ECM进行机械信号传导以在癌症、神经肌肉接头和心脏再生的背景下激活YAP/TAZ方面作用的观点。