Previous research in our laboratory found that inhibiting expression of vimentin, a marker of epithelial-to mesenchymal transition, inhibited cell growth and motility in vitro and in vivo. Tumors derived from vimentin knockdown cells showed features of epithelial redifferentiation and increased expression of differentiation-specific keratins. It is unknown what causes re-expression of keratins when vimentin is inhibited. Although, canonical Wnt signaling may activate NF-κB and repress of keratin and/or induce vimentin expression through β-catenin. We hypothesize that downregulation of differentiation-specific keratins contributes to tumor progression, mediated directly or indirectly by expression of vimentin. Vimentin-negative HN4 cells were transfected with plasmids encoding wild-type, PKCε-phosphomimetic, or unphosphorylatable versions of vimentin. Expression of vimentin was confirmed by western blot and immunofluorescence. Effects on cell growth and motility were determined using MTT, cell proliferation, and wound-closure assays. These results indicate that mutation of vimentin PKCε-phosphorylation sites cause changes in proliferation and filament assembly. Treatment of cells with an NF-κB inhibitor or 5-Aza-C, which allows re-expression of the Wnt inhibitor DKK3, led to a decrease in proliferation. These results suggest that inhibiting Wnt signaling removes the inhibition on GSK-3β and prevents activation of NF-κB, which decreases proliferation.
","abstract_html":"<p>Previous research in our laboratory found that inhibiting expression of vimentin, a marker of epithelial-to mesenchymal transition, inhibited cell growth and motility in vitro and in vivo. Tumors derived from vimentin knockdown cells showed features of epithelial redifferentiation and increased expression of differentiation-specific keratins. It is unknown what causes re-expression of keratins when vimentin is inhibited. Although, canonical Wnt signaling may activate NF-κB and repress of keratin and/or induce vimentin expression through β-catenin. We hypothesize that downregulation of differentiation-specific keratins contributes to tumor progression, mediated directly or indirectly by expression of vimentin. Vimentin-negative HN4 cells were transfected with plasmids encoding wild-type, PKCε-phosphomimetic, or unphosphorylatable versions of vimentin. Expression of vimentin was confirmed by western blot and immunofluorescence. Effects on cell growth and motility were determined using MTT, cell proliferation, and wound-closure assays. These results indicate that mutation of vimentin PKCε-phosphorylation sites cause changes in proliferation and filament assembly. Treatment of cells with an NF-κB inhibitor or 5-Aza-C, which allows re-expression of the Wnt inhibitor DKK3, led to a decrease in proliferation. These results suggest that inhibiting Wnt signaling removes the inhibition on GSK-3β and prevents activation of NF-κB, which decreases proliferation.</p>","abstract_has_math":false,"creators":["McGinn, Mary Catherine"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["W. Andrew Yeudall"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T05:53:18Z","subjects":["vimentin","keratin","oral cancer","Wnt signaling","Life Sciences","Physiology"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/49"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/49","href":"https://scholarscompass.vcu.edu/etd/49","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/4MZA-ZC05","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["W. Andrew Yeudall"]},{"key":"dc:creator","label":"Author","values":["McGinn, Mary Catherine"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-05-10T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["vimentin","keratin","oral cancer","Wnt signaling","Life Sciences","Physiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/4MZA-ZC05","https://scholarscompass.vcu.edu/etd/49"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Previous research in our laboratory found that inhibiting expression of vimentin, a marker of epithelial-to mesenchymal transition, inhibited cell growth and motility in vitro and in vivo. Tumors derived from vimentin knockdown cells showed features of epithelial redifferentiation and increased expression of differentiation-specific keratins. It is unknown what causes re-expression of keratins when vimentin is inhibited. Although, canonical Wnt signaling may activate NF-κB and repress of keratin and/or induce vimentin expression through β-catenin. We hypothesize that downregulation of differentiation-specific keratins contributes to tumor progression, mediated directly or indirectly by expression of vimentin. Vimentin-negative HN4 cells were transfected with plasmids encoding wild-type, PKCε-phosphomimetic, or unphosphorylatable versions of vimentin. Expression of vimentin was confirmed by western blot and immunofluorescence. Effects on cell growth and motility were determined using MTT, cell proliferation, and wound-closure assays. These results indicate that mutation of vimentin PKCε-phosphorylation sites cause changes in proliferation and filament assembly. Treatment of cells with an NF-κB inhibitor or 5-Aza-C, which allows re-expression of the Wnt inhibitor DKK3, led to a decrease in proliferation. These results suggest that inhibiting Wnt signaling removes the inhibition on GSK-3β and prevents activation of NF-κB, which decreases proliferation.
"]},{"key":"dc:title","label":"Title","values":["Interplay Between Keratin and Vimentin Expression in Oral Cancer"]}]}],"canonical_facts":{"dc:contributor":["W. Andrew Yeudall"],"dc:creator":["McGinn, Mary Catherine"],"dc:date.available":["2015-05-10T07:00:00Z"],"dc:description.abstract":["Previous research in our laboratory found that inhibiting expression of vimentin, a marker of epithelial-to mesenchymal transition, inhibited cell growth and motility in vitro and in vivo. Tumors derived from vimentin knockdown cells showed features of epithelial redifferentiation and increased expression of differentiation-specific keratins. It is unknown what causes re-expression of keratins when vimentin is inhibited. Although, canonical Wnt signaling may activate NF-κB and repress of keratin and/or induce vimentin expression through β-catenin. We hypothesize that downregulation of differentiation-specific keratins contributes to tumor progression, mediated directly or indirectly by expression of vimentin. Vimentin-negative HN4 cells were transfected with plasmids encoding wild-type, PKCε-phosphomimetic, or unphosphorylatable versions of vimentin. Expression of vimentin was confirmed by western blot and immunofluorescence. Effects on cell growth and motility were determined using MTT, cell proliferation, and wound-closure assays. These results indicate that mutation of vimentin PKCε-phosphorylation sites cause changes in proliferation and filament assembly. Treatment of cells with an NF-κB inhibitor or 5-Aza-C, which allows re-expression of the Wnt inhibitor DKK3, led to a decrease in proliferation. These results suggest that inhibiting Wnt signaling removes the inhibition on GSK-3β and prevents activation of NF-κB, which decreases proliferation.
"],"dc:identifier":["https://doi.org/10.25772/4MZA-ZC05","https://scholarscompass.vcu.edu/etd/49"],"dc:rights":["© The Author"],"dc:subject":["vimentin","keratin","oral cancer","Wnt signaling","Life Sciences","Physiology"],"dc:title":["Interplay Between Keratin and Vimentin Expression in Oral Cancer"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T05:53:18Z"}