Kim, Seon-YoungPark, Song-YiJang, Hwan-SeokPark, Yong-DooKee, Sun-Ho2021-10-092021-10-092021-10-092021-09-0110.3390/biomedicines9091264https://infoscience.epfl.ch/handle/20.500.14299/181972WOS:000699121400001Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-kappa B (NF-kappa B) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-kappa B signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.Biochemistry & Molecular BiologyMedicine, Research & ExperimentalPharmacology & PharmacyResearch & Experimental Medicinee-cadherinzo-1yapangiomotintight junctioncell migrationtext::journal::journal article::research article