The Piezo1 Mechanosensitive Ion Channel Promotes Melanoma Malignant Progression by Activating PI3K-AKT Signaling

Abstract

Background: Melanoma is a highly aggressive cancer that can metastasize at early stage. The mechanosensitive ion channel Piezo1 plays a crucial role in embryonic development, tumour growth, migration, invasion and vascularization. The aim of this study was to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma.Methods: The expression of Piezo1 in melanoma was analysed using quantitative real-time PCR and public databases. The effect of Piezo1 on cell viability was examined using a cell counting kit-8 assay. Cell invasion and migration ability were assessed using wound healing assays, transwell assays, transendothelial migration assays and a tail vein cancer metastasis model in vivo. Bioinformatics and western blot assayses were used to explore the effect of Pieoz1 on P13K/AKT signalling.Results: Piezo1 was upregulated in melanoma and was positively associated with poor survival. Piezo1 knockdown significantly weakened the intracellular calcium signal significantly and inhibited the viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the invasion and metastasis ability in vitro and in vivo by inducing the expression of cell cycle, invasion and metastasis related genes. To clarify the possible mechanism, it seems that Piezo1 activates the PI3K-AKT signalling to maintain malignant phenotypes of melanoma.Conclusion: Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

A Piez-o the jigsaw: the Piezo1 channel in skin biology

“…61 Mechanistically, Piezo1 seems to activate phosphoinositide-3-kinase-AKT signalling to promote the tumourigenicity of melanoma. 61 Moreover, Piezo1 appears to act as a mechanosensor for regulating melanoma migration during confinement: elongation of the migrating melanoma cell in a confined space induces Piezo1 activity to promote confined cell migration (Fig. 3).…”

“…Increased Piezo1 levels were found in primary and metastatic melanoma, and Piezo1 expression was associated with overall shorter survival 6 . Piezo1 inhibition in mouse and human melanoma cell lines and in a mouse metastasis tumour model led to the suppression of melanoma cell viability, invasion, transendothelial migration and expression of mesenchymal‐related genes (N‐cadherin and E‐cadherin) and invasion/metastasis‐related genes ( MMP2 and MMP9 ) 61 . Mechanistically, Piezo1 seems to activate phosphoinositide‐3‐kinase‐AKT signalling to promote the tumourigenicity of melanoma 61 .…”

“…6 Piezo1 inhibition in mouse and human melanoma cell lines and in a mouse metastasis tumour model led to the suppression of melanoma cell viability, invasion, transendothelial migration and expression of mesenchymal-related genes (N-cadherin and Ecadherin) and invasion/metastasis-related genes (MMP2 and MMP9). 61 Mechanistically, Piezo1 seems to activate phosphoinositide-3-kinase-AKT signalling to promote the tumourigenicity of melanoma. 61 Moreover, Piezo1 appears to act as a mechanosensor for regulating melanoma migration during confinement: elongation of the migrating melanoma cell in a confined space induces Piezo1 activity to promote confined cell migration (Fig.…”