title: Plakoglobin Reduces the in vitro Growth, Migration and Invasion of Ovarian Cancer Cells Expressing N-Cadherin and Mutant p53.
abstract: Aberrant expression of cadherins and catenins plays pivotal roles in ovarian cancer development and progression. Plakoglobin (PG, γ-catenin) is a paralog of β-catenin with dual adhesive and signaling functions. While β-catenin has known oncogenic function, PG generally acts as a tumor/metastasis suppressor. We recently showed that PG interacted with p53 and that its growth/metastasis inhibitory function may be mediated by this interaction. Very little is known about the role of PG in ovarian cancer. Here, we investigated the in vitro tumor/metastasis suppressor effects of PG in ovarian cancer cell lines with mutant p53 expression and different cadherin profiles. We showed that the N-cadherin expressing and E-cadherin and PG deficient ES-2 cells were highly migratory and invasive, whereas OV-90 cells that express E-cadherin, PG and very little/no N-cadherin were not. Exogenous expression of PG or E-cadherin or N-cadherin knockdown in ES-2 cells (ES-2-E-cad, ES-2-PG and ES-2-shN-cad) significantly reduced their migration and invasion. Also, PG expression or N-cadherin knockdown significantly decreased ES-2 cells growth. Furthermore, PG interacted with both cadherins and with wild type and mutant p53 in normal ovarian and ES-2-PG cell lines, respectively.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Alaee
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Ghazal
authors.initials: G
authors.lastname: Danesh
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Pasdar
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051185:gamma Catenin
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D051180:Desmoplakins; C495292:JUP protein, human; D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051185:gamma Catenin