Unknown

Dataset Information

0

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 regulation of Rho GTPase family proteins, enhancing cell migration. These YAP-dependent feedback loops result in a switch-like change in the signaling and the expression of EMT-related markers, leading to a robust enhancement in invasive cell spread, which may lead to a worsened clinical outcome in renal and other cancers.

SUBMITTER: Park J 

PROVIDER: S-EPMC6594963 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6461864 | biostudies-literature
| S-EPMC7156961 | biostudies-literature
| S-EPMC3147112 | biostudies-literature
| S-EPMC1761909 | biostudies-literature
| S-EPMC4884964 | biostudies-literature
| S-EPMC8564657 | biostudies-literature
| S-EPMC5951220 | biostudies-literature
| S-EPMC5047960 | biostudies-literature
| S-EPMC8124465 | biostudies-literature
| S-EPMC3705571 | biostudies-literature