title: Ezrin regulates cell-cell and cell-matrix adhesion, a possible role with E-cadherin/beta-catenin.
abstract: Ezrin, radixin, moesin and merlin form a subfamily of conserved proteins in the band 4.1 superfamily. The function of these proteins is to link the plasma membrane to the actin cytoskeleton. Merlin is defective or absent in schwannomas and meningiomas and has been suggested to function as a tumour suppressor. In this study, we have examined the role of ezrin as a potential regulator of the adhesive and invasive behaviour of tumour cells. We have shown that following inhibition of ezrin expression in colo-rectal cancer cells using antisense oligonucleotides, these cells displayed a reduced cell-cell adhesiveness together with a gain in their motile and invasive behaviour. These cells also displayed increased spreading over matrix-coated surfaces. Immunofluorescence studies revealed that antisense-treated cells also displayed an increased staining of paxillin in areas representing focal adhesions. Furthermore, coprecipitation studies revealed an association of ezrin with E-cadherin and beta-catenin. Induction of the phosphorylation of ezrin by orthovanadate and hepatocyte growth factor/scatter factor resulted in changes similar to those seen with antisense treatment, together with a marked decrease in the association of ezrin with both beta-catenin and E-cadherin. It is concluded that ezrin regulates cell-cell and cell-matrix adhesion, by interacting with cell adhesion molecules E-cadherin and beta-catenin, and may thus play an important role in the control of adhesion and invasiveness of cancer cells.
authors.affiliation: Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Hiscox
authors.forename: W G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D000099149:Ezrin
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D000099149:Ezrin; C495270:CTNNB1 protein, human