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
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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