Cell motility is controlled by the dynamic cytoskeleton and its related
proteins, such as members of the
ezrin/
radixin/
moesin (ERM) family, which act as signalling molecules inducing cytoskeleton remodelling. Although ERM
proteins have been identified as important factors in various
malignancies, functional redundancy between these
proteins has hindered the dissection of their individual contribution. The aim of the present study was to analyse the functional role of
moesin in pancreatic
malignancies.
Cancer cells of different malignant lesions of human and transgenic mice pancreata were evaluated by immunohistochemistry. For functional analysis, cell growth, adhesion and invasion assays were carried out after transient and stable knock-down of
moesin expression in
pancreatic cancer cells. In vivo tumourigenicity was determined using orthotopic and metastatic mouse tumour models. We now show that
moesin knock-down increases migration, invasion and
metastasis and influences extracellular matrix organization of
pancreatic cancer.
Moesin-regulated migratory activities of
pancreatic cancer cells were in part promoted through cellular translocation of
beta-catenin, and re-distribution and organization of the cytoskeleton. Analysis of human and different transgenic mouse
pancreatic cancers demonstrated that
moesin is a phenotypic marker for
anaplastic carcinoma, suggesting that this ERM
protein plays a specific role in pancreatic
carcinogenesis.