title: The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8.
abstract: Infection with viruses of the genus Betapapillomavirus, β-human papillomaviruses (β-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins β-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that β-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of β-catenin was elevated, no signs of β-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of β-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that β-catenin and ZO-1 are direct targets of E7 of the oncogenic β-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heuser
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hufbauer
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Marx
authors.affiliation: Department of Urology, University Hospital Cologne, Cologne, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Tok
authors.affiliation: Department of Dermatology and Venereology, Medical University in Warsaw, Warsaw, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Majewski
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Pfister
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: Baki
authors.initials: B
authors.lastname: Akgül
mesh_terms: D000818:Animals; D052686:Betapapillomavirus / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D008822:Mice, Transgenic; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D012867:Skin / Q000473:pathology; D062826:Zonula Occludens-1 Protein / Q000032:analysis*; D051176:beta Catenin / Q000032:analysis*
chemical_list: D050725:Papillomavirus E7 Proteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin