Cell crowding activates pro-invasive mechanotransduction pathway in high-grade DCIS via TRPV4 inhibition and cell volume reduction.

ABSTRACT: Cell crowding is a common microenvironmental factor influencing various disease processes, but its role in promoting cell invasiveness remains unclear. This study investigates the biomechanical changes induced by cell crowding, focusing on pro-invasive cell volume reduction in ductal carcinoma in situ (DCIS). Crowding specifically enhanced invasiveness in high-grade DCIS cells through significant volume reduction compared to hyperplasia-mimicking or normal cells. Mass spectrometry revealed that crowding selectively relocated ion channels, including TRPV4, to the plasma membrane in high-grade DCIS cells. TRPV4 inhibition triggered by crowding decreased intracellular calcium levels, reduced cell volume, and increased invasion and motility. During this process, TRPV4 membrane relocation prime

SUBMITTER: Bu X 

PROVIDER: S-EPMC12011371 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature