Preprint Highlight: Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells.

Abstract

Piezo1 is a mechanosensitive ion channel implicated in focal adhesion dynamics. This study investigates whether there is direct cross-talk between matrix mechanosensing and Piezo1 channel gating in normal and transformed cells. Live imaging, photobleaching, drug treatments, and gene knockdown approaches in human cell lines are used to characterize Piezo1's role at focal adhesions in 15 cell types. Piezo1 exhibits force-dependent recruitment and activates local calcium signals at focal adhesions to promote adhesion disassembly in normal cells but not in cancer cells. This work establishes a direct connection between two distinct mechanosensing systems, ion channels and cell–matrix adhesions. The role of Piezo1 in processes such as tumor angiogenesis and vascular development underscores the need to mechanistically understand its distinctive functions in normal versus cancer cells.