Progression of Oral Squamous Cell Carcinoma Accompanied with Reduced E-Cadherin Expression but Not Cadherin Switch

Abstract

The cadherin switch from E-cadherin to N-cadherin is considered as a hallmark of the epithelial-mesenchymal transition and progression of carcinomas. Although it enhances aggressive behaviors of adenocarcinoma cells, the significance and role of cadherin switch in squamous cell carcinomas (SCCs) are largely controversial. In the present study, we immunohistochemically examined expression of E-cadherin and N-cadherin in oral SCCs (n = 63) and its implications for the disease progression. The E-cadherin-positive carcinoma cells were rapidly decreased at the invasive front. The percentage of carcinoma cells stained E-cadherin at the cell membrane was reduced in parallel with tumor dedifferentiation (P<0.01) and enhanced invasion (P<0.01). In contrast, N-cadherin-positive cells were very limited and did not correlate with the clinicopathological parameters. Mouse tongue tumors xenotransplantated oral SCC cell lines expressing both cadherins in vitro reproduced the reduction of E-cadherin-positive carcinoma cells at the invasive front and the negligible expression of N-cadherin. These results demonstrate that the reduction of E-cadherin-mediated carcinoma cell-cell adhesion at the invasive front, but not the cadherin switch, is an important determinant for oral SCC progression, and suggest that the environments surrounding carcinoma cells largely affect the cadherin expression.

Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1

“…HMGA2 represses CDH1 expression through SNAI2 , ZEB2 , and TWIST1 (Li et al , 1997; Thuault et al , 2008), which were downregulated in wtMALT1 HSC2 cells. As numbers of previous studies established a fact that inactivation of E-cadherin ( CDH1 ) expression is a critical determinant for aggressive carcinomas (Hanahan and Weinberg, 2011; Hashimoto et al , 2012), expression status of MALT1 may have a great impact on oral carcinoma progression.…”

Clinical implications of epigenetic regulation in oral cancer

“…Meta-analysis data from 14 studies indicate increase in hypermethylation of CDH1 from normal healthy (19%), premalignant tissue (30%) and TAM (34%) to oral cancer (50%) ( Table 1). Hashimoto and colleagues observed loss of CDH1 expression due to hypermethylation in the increased invasive edge, indicating a critical role in oral cancer invasion [95].…”

Pattern of invasion in squamous cell carcinomas of the lower lip and oral cavity

“…These investigations suggested that the probability of complete EMT in OSCC is very low. 9,10 In line with these reports, Pod was used alongside E-and N-Cads to evaluate invasive patterns of OSCC and the results indicated the probability of CCI in these cancers. 3,11 A plethora of molecular pathways and markers is involved in the invasion of cancer cells, however the most popular proteins to define EMT and CCI have been the cadherin family, mesenchymal markers like vimentin and the trans-membrane glycoprotein Pod due to its possible role in CCI.…”