Kim Heon-Su, Suh Jung-Soo, Jang Yoon-Kwan, Ahn Sang-Hyun, Choi Gyu-Ho, Yang Jin-Young, Lim Gah-Hyun, Jung Youngmi, Jiang Jie, Sun Jie, Suk Myungeun, Wang Yingxiao, Kim Tae-Jin
Department of Integrated Biological Science, Pusan National University, Pusan, South Korea.
Institute of Systems Biology, Pusan National University, Pusan, South Korea.
Front Cell Dev Biol. 2022 May 13;10:865056. doi: 10.3389/fcell.2022.865056. eCollection 2022.
A mechanosensitive ion channel, Piezo1 induces non-selective cation flux in response to various mechanical stresses. However, the biological interpretation and underlying mechanisms of cells resulting from Piezo1 activation remain elusive. This study elucidates Piezo1-mediated Ca influx driven by channel activation and cellular behavior using novel Förster Resonance Energy Transfer (FRET)-based biosensors and single-cell imaging analysis. Results reveal that extracellular Ca influx Piezo1 requires intact caveolin, cholesterol, and cytoskeletal support. Increased cytoplasmic Ca levels enhance PKA, ERK, Rac1, and ROCK activity, which have the potential to promote cancer cell survival and migration. Furthermore, we demonstrate that Piezo1-mediated Ca influx upregulates membrane ruffling, a characteristic feature of cancer cell metastasis, using spatiotemporal image correlation spectroscopy. Thus, our findings provide new insights into the function of Piezo1, suggesting that Piezo1 plays a significant role in the behavior of cancer cells.
机械敏感离子通道Piezo1可响应各种机械应力诱导非选择性阳离子通量。然而，Piezo1激活所导致的细胞生物学解释及潜在机制仍不清楚。本研究使用基于新型荧光共振能量转移（FRET）的生物传感器和单细胞成像分析，阐明了通道激活驱动的Piezo1介导的Ca内流及细胞行为。结果显示，Piezo1介导的细胞外Ca内流需要完整的小窝蛋白、胆固醇和细胞骨架支持。细胞质Ca水平升高会增强PKA、ERK、Rac1和ROCK活性，这有可能促进癌细胞的存活和迁移。此外，我们使用时空图像相关光谱法证明，Piezo1介导的Ca内流会上调膜皱褶，这是癌细胞转移的一个特征。因此，我们的研究结果为Piezo1的功能提供了新的见解，表明Piezo1在癌细胞行为中起重要作用。
