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Involvement of the Wnt-β-catenin pathway in invasion and migration of oral squamous carcinoma cells

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The Wnt/β-catenin pathway plays a critical role in cell proliferation and oncogenesis. To clarify the role of cytoplasmic accumulation of β-catenin in oral squamous cell carcinoma (SCC), the cDNA of a mutant form of β-catenin that lacks the entire region with the glycogen synthase kinase-3 β (GSK-3β)-specific phosphorylation site was transfected into Ca9-22 cells whose β-catenin had been expressed predominantly at the membrane, and permanent cell lines expressing aberrant β-catenin in the cytoplasm and nucleus were produced. These transfectants, C1 and C5, proliferated at similar rates to the parental Ca9-22 cells, but the cell morphology changed from polygonal to spindle-shaped and close cell-cell interaction was lost. These mutant β-catenin-expressing cells exhibited a significantly higher invasion/migration capacity than wild-type Ca9-22 cells. The transcriptional activities of this mutant β-catenin form was enhanced in these cells which could be demonstrated by an elevated level of the transcription factor T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent reporter gene activity as well as by the up-regulation of Wnt/β-catenin target gene matrix metalloproteinase (MMP)-7. Moreover, we observed the redistribution of E-cadherin, the rearrangement of actin filaments, and the elevation of active Rho family members, Cdc42 and Rac. These results suggest that aberrant cytoplasmic accumulation of β-catenin can induce Tcf/Lef-mediated transcriptional activity, up-regulate MMP-7, and induce epithelial and mesenchymal transition (EMT). This would enhance the invasion and migration of oral SCC cells.
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Document Type: Research Article

Affiliations: Department of Oral and Maxillofacial Surgery II, Osaka University Graduated School of Dentistry, Suita, Osaka 565-0871, Japan., Email: [email protected]

Publication date: November 1, 2010

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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