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Involvement of the Wnt-β-catenin pathway in invasion and migration of oral squamous carcinoma cells.
- Source :
-
International journal of oncology [Int J Oncol] 2010 Nov; Vol. 37 (5), pp. 1095-103. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Blotting, Western
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Cell Line, Tumor
Cell Movement genetics
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic physiology
Humans
Lymphoid Enhancer-Binding Factor 1 biosynthesis
Lymphoid Enhancer-Binding Factor 1 genetics
Matrix Metalloproteinase 7 biosynthesis
Matrix Metalloproteinase 7 genetics
Mouth Neoplasms genetics
Mouth Neoplasms pathology
Neoplasm Invasiveness pathology
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Carcinoma, Squamous Cell metabolism
Mouth Neoplasms metabolism
Neoplasm Invasiveness genetics
Signal Transduction physiology
Wnt Proteins metabolism
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 37
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20878057
- Full Text :
- https://doi.org/10.3892/ijo_00000761