Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling

Abstract

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis

“…It was interesting that with the treatment of cyclic straining, the positive effect on A375 cells was greater than on B16 cells. In a previous report, after the interference of mechanosensing ion channel Piezo 1, the proliferation ability of melanoma cells was inhibited [ 35 ]. Specifically, the decreased positive ratio of Ki67 in A375 cells was greater than the decreased value in B16 cells.…”

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

“…We, however, know that the dynamic endosomal‐PM translocation of TRPV2, regulating its activity (Kojima & Nagasawa, 2014 ), can be induced by mechanical cues (Karki & Tojkander, 2021 ). The cAMP‐dependent protein kinase A (PKA) and the PI3K/AKT pathways have been shown to regulate TRPV2 trafficking to the PM (Stokes et al , 2004 ; Nagasawa & Kojima, 2015 ), and intriguingly both pathways are, respectively, negatively or positively regulated by PIEZO1 (Hung et al , 2016 ; Zhang et al , 2022 ), a stretch‐activated channel involved in adhesion maturation and confinement‐induced migration (Canales Coutino & Mayor, 2021 ; Yao et al , 2022 ; Zhang et al , 2022 ).…”