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dc.contributor.advisorStack, M. Sharon, 1959-eng
dc.contributor.authorJiang, Rongeng
dc.date.issued2010eng
dc.date.submitted2010 Summereng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on November 9, 2010).eng
dc.descriptionVita.eng
dc.description"July 2010"eng
dc.descriptionThesis advisor: M. Sharon Stack.eng
dc.descriptionM.S. University of Missouri-Columbia 2010.eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Oral squamous cell carcinoma (OSCC) is one of the top 10 causes of cancer deaths worldwide, with a 50% 5-year survival rate, necessitating the discovery of novel biomarkers. Using cDNA microarray analyses, we identified expression of a panel of kallikreins (KLK 5, 7, 8, and 10) associated with formation of more aggressive OSCC tumors in a murine orthotopic OSCC model. In initial studies, KLK levels in malignant OSCC cells (SCC25) were compared to cells from normal oral mucosa (OKF) using qPCR. A marked elevation of all KLKs was observed in aggressive SCC25 cells relative to OKF cells. In normal skin, KLKs 5, 7, and 8 are involved in desquamation during epidermal differentiation via proteolytic cleavage of the desmosomal cadherin component desmoglein 1 (Dsg1). As loss of cell-cell adhesion is prevalent in tumor metastasis, Dsg1 was evaluated by immunofluorescence and western blotting. SCC25 cells exhibit cleavage of Dsg1 which is blocked by treatment with a KLK inhibitor as well as by siRNA silencing of KLK5. Furthermore, cell-cell adhesion and barrier function assays demonstrate that silencing of KLK5 enforces cell-cell adhesion and improves epithelial barrier function; overexpression of KLK5 in normal oral mucosal cells (OKF) reduces cell-cell adhesion and affects epithelial barrier function. These data suggest that KLK5 may promote metastatic dissemination of OSCC by promoting loss of junctional integrity through cleavage of desmoglein 1.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.format.extentviii, 74 pageseng
dc.identifier.merlinb81106415eng
dc.identifier.oclc680025753eng
dc.identifier.urihttps://hdl.handle.net/10355/9528
dc.identifier.urihttps://doi.org/10.32469/10355/9528eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campuses of the University of Missouri.eng
dc.subject.meshCarcinoma, Squamous Cell -- metabolismeng
dc.subject.meshKallikreins -- biosynthesiseng
dc.subject.meshDesmoglein 1 -- metabolismeng
dc.subject.meshMouth Neoplasms -- metabolismeng
dc.subject.meshGene Expression Regulation, Neoplasticeng
dc.subject.meshDisease Progressioneng
dc.subject.meshCell Adhesioneng
dc.titleKallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinomaeng
dc.typeThesiseng
thesis.degree.disciplinePathology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelMasterseng
thesis.degree.nameM.S.eng


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