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

• Main Authors: Biqiang Zhu, Wei Qian, Chaoqun Han, Tao Bai, Xiaohua Hou
• Format: Article
• Language: English
• Published: Elsevier 2021-06-01
• Series: Molecular Therapy: Nucleic Acids
• Subjects: cholangiocarcinoma; metastasis; Piezo 1; Yes-associated protein 1; epithelial-to-mesenchymal transition
• Online Access: http://www.sciencedirect.com/science/article/pii/S2162253121000615

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 in vitro and in vivo. 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.