Linking Extracellular Matrix Agrin to the Hippo Pathway in Liver Cancer and Beyond.

Linking Extracellular Matrix Agrin to the Hippo Pathway in Liver Cancer and Beyond.
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DOI:
10.3390/cancers10020045
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发表时间:
2018-02-06
期刊:
影响因子:
5.2
通讯作者:
Hong W
Hong W
中科院分区:
医学2区
文献类型:
--
作者:
Chakraborty S;Hong W

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除了结构和支架作用外,细胞外基质(ECM)正在成为生物力学信号转导的中心,该信号转导经常被传递到细胞内传感器以调节不同的细胞过程。在宏观尺度上,基质刚性赋予有助于组织纤维化和癌症的长期效应。转录共激活因子雅普/TAZ是Hippo信号通路的会聚效应子,因其在器官稳态和癌症中作为核机械传感器的新作用而被广泛认可。尽管如此,雅普/TAZ如何从ECM中感知这些“僵硬的线索”仍然是个谜。在这里,我们强调了最近的观点,聚集蛋白的作用,从ECM通过拮抗海马通路激活雅普/TAZ的背景下,癌症,神经肌肉接头,心脏再生。
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.
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