Park, JinSeok Kim, Deok-Ho Shah, Sagar R. Kim, Hong-Nam Kshitiz Kim, Peter Quinones-Hinojosa, Alfredo Levchenko, Andre 2024-01-19T20:02:05Z 2024-01-19T20:02:05Z 2021-09-02 2019-06 2041-1723 https://pubs.kist.re.kr/handle/201004/119961 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. English Nature Publishing Group Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases Article 10.1038/s41467-019-10729-5 1 Nature Communications, v.10 Nature Communications 10 Y scie scopus 000472840400012 2-s2.0-85068026123 Multidisciplinary Sciences Science & Technology - Other Topics Article COLLECTIVE CELL-MIGRATION MEDIATES CONTACT INHIBITION E-CADHERIN MECHANICAL-PROPERTIES TOPOGRAPHIC GUIDANCE FOCAL ADHESIONS WILMS-TUMOR ACTIVATION COMPLEX YAP/TAZ