Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases
Autor: | David H. Ellison, Deok Ho Kim, Sagar R. Shah, Kshitiz, Hong Nam Kim, Alfredo Quinones-Hinojosa, JinSeok Park, Andre Levchenko, Peter S. Kim, Kahp-Yang Suh |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
rho GTP-Binding Proteins
0301 basic medicine Epithelial-Mesenchymal Transition Surface Properties Science Green Fluorescent Proteins General Physics and Astronomy 02 engineering and technology GTPase Feedback regulation Article General Biochemistry Genetics and Molecular Biology Madin Darby Canine Kidney Cells Extracellular matrix 03 medical and health sciences Dogs Cell Behavior (q-bio.CB) medicine Extracellular Animals Epithelial–mesenchymal transition WT1 Proteins lcsh:Science Adaptor Proteins Signal Transducing Multidisciplinary Chemistry technology industry and agriculture Epithelial Cells Cell migration General Chemistry 021001 nanoscience & nanotechnology Epithelium Nanostructures Cell biology 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques FOS: Biological sciences embryonic structures Quantitative Biology - Cell Behavior lcsh:Q 0210 nano-technology Wound healing Cell signalling |
Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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. Reorganisation of the extracellular matrix (ECM) controls processes involving epithelial-mesenchymal transition (EMT). Here, the authors show that EMT occurring in epithelial cells on a fabricated nano-engineered cell adhesion surface is triggered by mechanical cues from the ECM. |
Databáze: | OpenAIRE |
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