Concomitant loss of p120-catenin and β-catenin membrane expression and oral carcinoma progression with E-cadherin reduction.

Abstract

The binding of p120-catenin and β-catenin to the cytoplasmic domain of E-cadherin establishes epithelial cell-cell adhesion. Reduction and loss of catenin expression degrades E-cadherin-mediated carcinoma cell-cell adhesion and causes carcinomas to progress into aggressive states. Since both catenins are differentially regulated and play distinct roles when they dissociate from E-cadherin, evaluation of their expression, subcellular localization and the correlation with E-cadherin expression are important subjects. However, the same analyses are not readily performed on squamous cell carcinomas in which E-cadherin expression determines the disease progression. In the present study, we examined expression and subcellular localization of p120-catenin and β-catenin in oral carcinomas (n = 67) and its implications in the carcinoma progression and E-cadherin expression using immunohitochemistry. At the invasive front, catenin-membrane-positive carcinoma cells were decreased in the dedifferentiated (p120-catenin, P < 0.05; β-catenin, P < 0.05) and invasive carcinomas (p120-catenin, P < 0.01; β-catenin, P < 0.05) and with the E-cadherin staining (p120-catenin, P < 0.01; β-catenin, P < 0.01). Carcinoma cells with β-catenin cytoplasmic and/or nuclear staining were increased at the invasive front compared to the center of tumors (P < 0.01). Although the p120-catenin isoform shift from three to one associates with carcinoma progression, it was not observed after TGF-β, EGF or TNF-α treatments. The total amount of p120-catenin expression was decreased upon co-treatment of TGF-β with EGF or TNF-α. The above data indicate that catenin membrane staining is a primary determinant for E-cadherin-mediated cell-cell adhesion and progression of oral carcinomas. Furthermore, it suggests that loss of p120-catenin expression and cytoplasmic localization of β-catenin fine-tune the carcinoma progression.

• Authors: Kazunobu Sasaya, Haruka Sudo, Genta Maeda, Shuichi Kawashiri, Kazushi Imai
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e69777 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23936352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Catenins
• beta Catenin
• Delta Catenin
• CTNND1 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Cadherins (metabolism)
• Catenins (metabolism)
• Cell Line, Tumor
• Cell Membrane (drug effects, metabolism)
• Disease Progression
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Intracellular Space (drug effects, metabolism)
• Middle Aged
• Mouth Neoplasms (metabolism, pathology)
• Protein Transport (drug effects)
• beta Catenin (metabolism)
• Delta Catenin