PIEZO1 Affects Cell Growth and Migration via Microfilament-Mediated YAP trans-Latitudinal Regulation

Environmental mechanical forces, such as cell membrane stress, cell extrusion, and stretch, have been proven to affect cell growth and migration. Piezo1, a mechanosensitive channel protein, responds directly to endogenous or exogenous mechanical stimuli. Here, we explored the Piezo1 distribution and microfilament morphological changes induced by mechanical forces in the tumor and normal cells. In addition, Piezo1 activation in tumor cells resulted in the nuclear accumulation of YAP, whereas nuclear export of YAP and microfilament depolymerization occurred with the prolonged activation, while a removal stimulation restored the YAP distribution and microfilament polymerization. Combining the morphological changes of the microfilament under Piezo1 activation and the function of YAP in regulating cell growth and development, we suggest that Piezo1 senses changes in environmental mechanical forces and regulates YAP distribution through the microfilament cytoskeleton network, which in turn affects the growth and migration more obviously in tumor cells rather than normal cells. Our results are essential for understanding the trans-latitudinal transmission of mechanical forces and exploring the role of environmental mechanical forces in tumor therapy.