The expression and phosphorylation of ezrin and merlin in human pancreatic cancer

Abstract

Pancreatic carcinoma is the most common pancreatic malignancy and is associated with a very poor prognosis. Therefore, new prognostic factors and new treatment strategies are clearly needed. In this study, we retrospectively studied the levels of phosphorylated ezrin in 19 patients with pancreatic carcinoma by immunohistochemical analysis and determined the correlation between protein expression, clinicopathological characteristics and prognosis in pancreatic adenocarcinoma. We also characterized the phenotype of the overexpression of wild-type and phosphorylated ezrin and merlin in human pancreatic cancer cell lines. A significant correlation between the levels of phosphorylated ezrin353 and ezrin567 and the stage of pancreatic cancer was observed. Moreover, Kaplan-Meier analysis revealed that patients with high levels of phosphorylated ezrin had a significantly poorer survival rate (P<0.05). In addition, the overexpression of wild-type merlin or ezrin inhibited cell proliferation, migration and adhesion. However, the overexpression of T567D ezrin, a mutant that mimics permanent phosphorylation, promoted the proliferation, adhesion and migration of the pancreatic adenocarcinoma cell line SW1990. The overexpression of S518D merlin inhibited the growth of SW1990 and did not affect migration or adhesion. These results suggest that the phosphorylation of ezrin may contribute to the progression of pancreatic carcinoma and that the level of phosphorylated ezrin may serve as an adverse prognostic factor for pancreatic carcinoma.