Mechanosensitive ion channel Piezo1 promotes prostate cancer development through the activation of the Akt/mTOR pathway and acceleration of cell cycle

摘要

Prostate cancer is one of the most common types of cancer affecting men worldwide; however, its etiology and pathological mechanisms remain poorly understood. Mechanical stimulation plays a key role in prostate cancer development. Piezo type mechanosensitive ion channel component 1 (Piezo1), which functions as a cell sensor and transducer of mechanical stimuli, may have a crucial role in the development of prostate cancer. In the present study, the expression of the Piezo1 channel was demonstrated to be significantly elevated in prostate cancer cell lines and in human prostate malignant tumor tissues. Downregulation of Piezo1 significantly suppressed the viability, proliferation and migration of prostate cancer cells in vitro , and inhibited prostate tumor growth in vivo . The activation of the Akt/mTOR pathway or acceleration of cell cycle progression from G _(0)/G _(1) to S phase may downstream consequences of Piezo 1 signal pathway activation. Downregulation of Piezo1 considerably suppressed Ca ~(2+) signal increments, inhibited the phosphorylation of Akt and mTOR and arrested the cell cycle of prostate cancer cells at G _(0)/G _(1) phase in while inhibiting the activation of CDK4 and cyclin D1. Taken together, these findings suggest that Piezo1 channels have a crucial role in prostate cancer development and may, therefore, be a novel therapeutic target in the treatment of prostate cancer.