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Proteinase Suppression by E-Cadherin-Mediated Cell-Cell Attachment in Premalignant Oral Keratinocytes.
journal contribution
posted on 2022-09-28, 00:00 authored by Hidayatullah G Munshi, Kathleen J Green, Sharon StackSharon Stack, Ratna Sen, Subhendu Mukhopadhyay, Supurna Ghosh, Yi I WuThe expression and activity of epithelial proteinases is under stringent control to prevent aberrant hydrolysis of structural proteins and disruption of tissue architecture. E-cadherin-dependent cell-cell adhesion is also important for maintenance of epithelial structural integrity,and loss of E-cadherin expression has been correlated with enhanced invasive potential in multiple tumor models. To address the hypothesis that there is a functional link between E-cadherin and proteinase expression,we have examined the role of E-cadherin in proteinase regulation. By using a calcium switch protocol to manipulate junction assembly,our data demonstrate that initiation of de novo E-cadherin-mediated adhesive contacts suppresses expression of both relative matrix metalloproteinase-9 levels and net urinary-type plasminogen activator activity. E-cadherin-mediated cell-cell adhesion increases both phosphatidylinositol 3'-kinase (PI3-kinase)-dependent AKT phosphorylation and epidermal growth factor receptor-dependent MAPK/ERK activation. Pharmacologic inhibition of the PI3-kinase pathway,but not the epidermal growth factor receptor/MAPK pathway,prevents E-cadherin-mediated suppression of proteinases and delays junction assembly. Moreover,inhibition of junction assembly with a function-blocking anti-E-cadherin antibody stimulates proteinase-dependent Matrigel invasion. As matrix metalloproteinase-9 and urinary-type plasminogen activator potentiate the invasive activity of oral squamous cell carcinoma,these data suggest E-cadherin-mediated signaling through PI3-kinase can regulate the invasive behavior of cells by modulating proteinase secretion.
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2022-09-29Language
- English
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Journal of Biological ChemistryUsage metrics
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