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Piezo 1激活通过Hippo/YAP信号轴促进胆管癌转移。

Piezo 1 activation facilitates cholangiocarcinoma metastasis via Hippo/YAP signaling axis.

作者信息

Zhu Biqiang, Qian Wei, Han Chaoqun, Bai Tao, Hou Xiaohua

机构信息

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Mol Ther Nucleic Acids. 2021 Feb 26;24:241-252. doi: 10.1016/j.omtn.2021.02.026. eCollection 2021 Jun 4.

DOI:10.1016/j.omtn.2021.02.026
PMID:33767919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7973248/
Abstract

Tumor metastasis is one of the major factors for the high mortality in cholangiocarcinoma (CCA), but its underlying mechanisms are not fully understood. Here, we report that Piezo-type mechanosensitive ion channel component 1 (Piezo 1) is detected to be significantly upregulated in CCA tissues, which is linked to a poor prognosis in patients, suggesting that Piezo 1 may act in a pro-metastatic role in CCA development. Piezo 1 is activated through 20% simulated physiological stretch, and deleting Piezo 1 impedes epithelial-to-mesenchymal transition (EMT) of CCA cells, as well as impairing their metastatic capacity and . Mechanistically, the activation of Piezo 1 results in large amounts of Yes-associated protein 1 (YAP) translocated into the nucleus from the cytoplasm, and thus the motility of CCA cells is significantly increased. These findings indicate that mechanical stimulation induces Piezo 1 activation, which might be involved in CCA metastasis via the Hippo/YAP signaling axis. Therefore, Piezo 1 and its downstream effectors may be a novel therapeutic target for CCA treatment.

摘要

肿瘤转移是胆管癌（CCA）高死亡率的主要因素之一，但其潜在机制尚未完全明确。在此，我们报告，在CCA组织中检测到压电型机械敏感离子通道蛋白1（Piezo 1）显著上调，这与患者预后不良相关，提示Piezo 1可能在CCA发展中发挥促转移作用。Piezo 1通过20%模拟生理拉伸被激活，敲除Piezo 1可阻碍CCA细胞的上皮-间质转化（EMT），并损害其转移能力。机制上，Piezo 1的激活导致大量Yes相关蛋白1（YAP）从细胞质转位至细胞核，从而显著增加CCA细胞的运动能力。这些发现表明，机械刺激诱导Piezo 1激活，其可能通过Hippo/YAP信号轴参与CCA转移。因此，Piezo 1及其下游效应分子可能是CCA治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/558a8dcd5886/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/5c6b5e93c021/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/74ed93dee401/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/496661e49461/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/a23b9684380f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/60e1703e0ab0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/7d9577e14742/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/558a8dcd5886/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/5c6b5e93c021/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/74ed93dee401/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/496661e49461/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/a23b9684380f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/60e1703e0ab0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/7d9577e14742/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/884d/7973248/558a8dcd5886/gr6.jpg

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