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

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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.
Funding Information
  • National Natural Science Foundation of China (82072702)
  • National Natural Science Foundation of China (81872008)
  • the Science and Technology Innovation as a Whole Plan Projects of Shaanxi Province, China (No. 2016KJZDSF01-05-01)
  • National Key R& D Projects Sub-project (No.2019YFC1315900)

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