Mechano-Sensing Channel PIEZO2 Enhances Invasive Phenotype in Triple-Negative Breast Cancer.

BACKGROUND

Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca channels, and cell depolarization. This study aimed to investigate PIEZO2's role in breast cancer.

METHODS

The clinical relevance of expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing overexpressed breast cancer cells, and and experiments were conducted.

RESULTS

High expression of was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in overexpressed cells after mechanical stimulation. overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of was correlated with the increased expression of epithelial-mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in overexpressed TNBC cells. overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation.

CONCLUSION

PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.