Activation of WNT Family Expression and Signaling in Squamous Cell Carcinomas of the Oral Cavity

• Published in: Journal of dental research Vol. 83; no. 4; pp. 327 - 332
• Main Authors: Uraguchi, M., Morikawa, M., Shirakawa, M., Sanada, K., Imai, K.
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01.04.2004; SAGE PUBLICATIONS, INC
• Subjects: beta Catenin; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cytoskeletal Proteins - metabolism; Dentistry; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Multigene Family; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Signal Transduction; Trans-Activators - metabolism; Tumor Cells, Cultured; Wnt Proteins; Zebrafish Proteins; β-catenin; oral carcinoma; invasion; WNT; EMT
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910408300411

The WNT family activates an oncogenic signaling mediated through β-catenin and is up-regulated in a variety of malignant neoplasms. The signaling translocates β-catenin into the nucleus and stimulates carcinoma cells in the epithelial-mesenchymal transition (EMT). However, WNT expression and signaling in oral carcinomas have not been examined. The present study focused on unveiling the involvement of WNTs in oral carcinomas, and showed that carcinoma cells express 11 of 19 WNT family members by reverse-transcription/PCR. WNT-expressing carcinoma cells exhibited increased β-catenin levels in the cytoplasmic pool and translocation to the nucleus. The activation state of signaling correlated with the expression of membrane-type 1 matrix metalloproteinase, which degrades territorial matrices in carcinoma invasion. Immunohistochemistry disclosed that WNT3 expression and nuclear localization of β-catenin were predominant in carcinoma cells at the invasive front. These results suggest that enhanced WNT expression and signaling accelerate the progression of carcinomas via activating EMTs and local invasiveness.