Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases.

ABSTRACT: Collective cell migration occurs in many patho-physiological states, including wound healing and invasive cancer growth. The integrity of the expanding epithelial sheets depends on extracellular cues, including cell-cell and cell-matrix interactions. We show that the nano-scale topography of the extracellular matrix underlying epithelial cell layers can strongly affect the speed and morphology of the fronts of the expanding sheet, triggering partial and complete epithelial-mesenchymal transitions (EMTs). We further demonstrate that this behavior depends on the mechano-sensitivity of the transcription regulator YAP and two new YAP-mediated cross-regulating feedback mechanisms: Wilms Tumor-1-YAP-mediated downregulation of E-cadherin, loosening cell-cell contacts, and YAP-TRIO-Merlin mediated

SUBMITTER: Park J 

PROVIDER: S-EPMC6594963 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature