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.

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Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca homeostasis, the underlying mechanisms have not been fully explored. In this study, we investigated the effects of amylin on rat hippocampal neurons using calcium imaging and whole-cell patch clamp recordings. We demonstrated that the amylin receptor antagonist AC187 abolished the Ca response induced by low concentrations of human amylin (hAmylin). However, the Ca response induced by higher concentrations of hAmylin was independent of the amylin receptor. This effect was dependent on extracellular Ca. Additionally, blockade of L-type Ca channels partially reduced hAmylin-induced Ca response. In whole-cell recordings, hAmylin depolarized the membrane potential. Moreover, application of the transient receptor potential (TRP) channel antagonist ruthenium red (RR) attenuated the hAmylin-induced increase in Ca. Single-cell RT-PCR demonstrated that transient receptor potential vanilloid 4 (TRPV4) mRNA was expressed in most of the hAmylin-responsive neurons. In addition, selective knockdown of TRPV4 channels inhibited the hAmylin-evoked Ca response. These results indicated that different concentrations of hAmylin act through different pathways. The amylin receptor mediates the excitatory effects of low concentrations of hAmylin. In contrast, for high concentrations of hAmylin, hAmylin aggregates precipitated on the neuronal membrane, activated TRPV4 channels and subsequently triggered membrane voltage-gated calcium channel opening followed by membrane depolarization. Therefore, our data suggest that TRPV4 is a key molecular mediator for the cytotoxic effects of hAmylin on hippocampal neurons.

This study demonstrates that flavonoids inhibit TMEM16A currents and suggests that flavonoids could have anticancer effects via this mechanism.