Matrix Stiffness Induces Epithelial-to-Mesenchymal Transition Via Piezo1-Regulated Calcium Flux

Abstract

Cells utilize calcium channels as one of the main signaling mechanisms to sense changes in the extracellular space and convert these changes to intracellular signals. The current study expands on the understanding of how EMT is controlled via the mechanosensitive ion channel Piezo1 in cancerous cells, which sense changes in the extracellular matrix stiffness. Herein, we model the biophysical environment of healthy and cancerous prostate tissue using polyacrylamide (PA) gels of different stiffnesses coated with collagen I. Significant changes in calcium influx, vimentin expression, and actin polymerization were observed in the high stiffness groups compared to the cells on low stiffness substrates. Additionally, these same differences were observed when PC3 and DU145 cells were grown on soft substrates while being treated with Yoda1, a chemical agonist of Piezo1. Overall, this study concludes that Piezo1 regulated calcium flux plays a role in prostate cancer cell metastatic potential by sensing changes in ECM stiffness and modulating EMT markers.