The activation of Piezo1 channel promotes invasion and migration via the release of extracellular ATP in cervical cancer.

ABSTRACT

BACKGROUND: The mechanosensitive ion channel Piezo1 has emerged as a potential prognostic and therapeutic target in different types of cancers. The aim of this study was to determine the expression levels and underlying mechanisms of Piezo1 in the invasion and migration processes in cervical cancer. METHODS: Initially, we employed qRT-PCR, western blot, and immunohistochemical staining techniques to assess the disparity in Piezo1 expression in cervical cancer tissues and cells. Subsequently, we conducted wound healing, transwell assays and phalloidin staining to observe the effects of stable Piezo1 silencing and Piezo1 selective agonist Yoda1 on the invasion and migration capabilities. The release of extracellular ATP was assessed using the enhanced ATP assay kit. Furthermore, we conducted rescue experiments to investigate whether the activation of Piezo1 facilitates cervical cancer invasion and migration through extracellular ATP. Finally, we constructed xenograft tumor models to determine weather the Piezo1 selective agonist Yoda1 influenced the tumor growth in vivo. RESULTS: In our study, we found that Piezo1 expression was elevated in both cervical cancer tissues and cells, with the highest levels observed in patients with lymph node metastasis. Knocking down Piezo1 resulted in a significant reduction in the invasion and migration capabilities of cervical cancer cells, whereas the use of the Piezo1 selective agonist Yoda1 enhanced these capabilities. Moreover, the activation of Piezo1 channels was found to regulate the release of extracellular ATP. Mechanistically, the activation of Piezo1 might facilitate cervical cancer invasion, migration, and pseudopodium formation through the release of extracellular ATP. And Piezo1 was an important molecule for the tumor growth of cervical cancer in vivo. CONCLUSION: Our findings revealed that Piezo1 facilitated the invasion and migration of cervical cancer by releasing extracellular ATP, which might hold potential as a valuable target for prognostic and therapeutic interventions in cervical cancer.