title: The physical interaction of p53 and plakoglobin is necessary for their synergistic inhibition of migration and invasion.
abstract: Plakoglobin (PG) is a paralog of β-catenin with similar adhesive, but contrasting signalling functions. Although β-catenin has well-known oncogenic function, PG generally acts as a tumor/metastasis suppressor by mechanisms that are just beginning to be deciphered. Previously, we showed that PG interacted with wild type (WT) and a number of mutant p53s, and that its tumor/metastasis suppressor activity may be mediated, at least partially, by this interaction. Here, carcinoma cell lines deficient in both p53 and PG (H1299), or expressing mutant p53 in the absence of PG (SCC9), were transfected with expression constructs encoding WT and different fragments and deletions of p53 and PG, individually or in pairs. Transfectants were characterized for their in vitro growth, migratory and invasive properties and for mapping the interacting domain of p53 and PG. We showed that when coexpressed, p53-WT and PG-WT cooperated to decrease growth, and acted synergistically to significantly reduce cell migration and invasion. The DNA-binding domain of p53 and C-terminal domain of PG mediated p53/PG interaction, and furthermore, the C-terminus of PG played a central role in the inhibition of invasion in association with p53.
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: Amarjot
authors.initials: A
authors.lastname: Padda
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Vahedah
authors.initials: V
authors.lastname: Mehrabani
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Lucas
authors.initials: L
authors.lastname: Churchill
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Pasdar
mesh_terms: D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism
chemical_list: C495292:JUP protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051185:gamma Catenin
keywords: invasion; migration; p53; plakoglobin; tumor/metastasis suppressor