Piezo1 activation facilitates ovarian cancer metastasis via Hippo/YAP signaling axis

Abstract

Ovarian cancer (OC) is a highly malignant cancer with great metastatic potential. Here we aimed to investigate the role of Piezo1, a gene related to the mechanical environment of the tumor, in promoting the metastasis of OC. We performed Piezo1 knockdown in A-1847 cells using small hairpin RNAs, and the cells were inoculated subcutaneously in nude mice. Piezo1 knockdown decreased the tumor growth rate of OC tumor xenografts in mice and reduced cell migration in vitro . Metastasis in the lung was also attenuated after Piezo1 knockdown as revealed by HE staining of the lung tissues, which was concomitant with downregulation of E-Cadherin and vimentin and upregulation of N-Cadherin analyzed using western blot analysis, suggesting suppressed epithelial-to-mesenchymal transition. Migration of Piezo1-knockdown cells was also analyzed for their migratory capabilities using the scratch assay. We also analyzed the key proteins in the Hippo/YAP signaling pathway using western blot after treating A-1847 and 3AO cells with a Piezo1 inducer, Yoda1. Piezo1 inducer Yoda1 activated Hippo/YAP signal in OC cells. In conclusion, Piezo1 is overexpressed in OC tissues and contributes to OC tumor growth and metastasis. Suppression of Piezo1 is a potential therapeutic strategy for OC.

The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment

“…Piezo1 is a stretch-activated ion channel that converts mechanical forces into cellular signaling through an influx of Ca 2+ ( 49 ). Similar to others ( 50 ), we found Piezo1 expressed in HGSOC tumors but did not observe changes in Piezo1 expression in response to stiffness (Fig. 3).…”

“…On the basis of our in vitro findings, we next asked how loss of PIEZO1 would affect tumor progression in vivo. A recent study found that PIEZO1 knockdown in A1847 ovarian cancer cells slowed tumor growth and metastasis; however, this study used a subcutaneous xenograft ( 50 ) rather than an intraperitoneal xenograft that better mimics the patient’s tumor microenvironment ( 37 ). We focused our analysis on the visceral fat deposits commonly involved in advanced HGSOC—the omentum (~80% of patients with stage III/IV HGSOC) and the mesentery (~30% of patients with stage III/IV HGSOC) ( 59 ).…”

PIEZO Ion Channels in Cardiovascular Functions and Diseases

“…The YAP and TAZ (transcriptional coactivator with PDZ-binding motif) transcription factors read and translate a broad range of mechanical cues into cell-specific transcriptional programs. 193 The PIEZO1-YAP axis has a key role in cancer metastasis, 194,195 neuronal specification in human neural stem cells, 196 and bone homeostasis in osteoblastic cells. 197 In aortic valve, interstitial cells the PIEZO1-YAP axis promotes osteogenic differentiation that contributes to calcific aortic valve disease 198 and mediates the endothelial atherogenic inflammatory response in ECs.…”

Pleiotropic physiological functions of Piezo1 in human body and its effect on malignant behavior of tumors

“…The Piezo1-HIF-1α-VEGF pathway ( Sun YH. et al, 2020 ; Wang et al, 2021 ), Piezo1-Src-YAP axis ( Kim O-H. et al, 2022 ), and Piezo1-LAST1/2-YAP axis ( Xiong et al, 2022 ) are all potential mechanisms of tumor metastasis. However, some studies have also proposed opposite conclusions.…”