Matrix stiffness induces epithelial-to-mesenchymal transition via Piezo1-regulated calcium flux in prostate cancer cells

Cells utilize calcium channels as one of the main signaling mechanisms to sense changes in the extracellular space and convert these changes to intracellular sig-nals. Calcium regulates several key signaling networks, such as the induction of EMT. The current study expands on the understanding of how EMT is controlled via the mechanosensitive calcium channel Piezo1 in cancerous cells, which senses changes in the extracellular matrix stiffness. We model the biophysical environ-ment of healthy and cancerous prostate tissue using polyacrylamide gels of different stiffnesses. Significant increases in calcium steady-state concentration, vimentin expression, and aspect ratio, and decreases in E-cadherin expression were observed by increasing matrix stiffness and also after treatment 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.

Automated summary

Cells use calcium channels to sense changes in the extracellular space and convert them into intracellular signals. The current study explores how EMT is controlled in cancer cells by the mechanosensitive calcium channel Piezo1, which senses changes in extracellular matrix stiffness. By modeling the biophysical environment of healthy and cancerous prostate tissue, the study shows that increased matrix stiffness and activation of Piezo1 cause significant changes in calcium concentration, vimentin expression, aspect ratio, and E-cadherin expression. In conclusion, Piezo1-regulated calcium flux plays a role in prostate cancer cell metastasis by sensing changes in ECM stiffness and modulating EMT markers.