title: Interaction between the human papillomavirus 16 E7 oncoprotein and gelsolin ignites cancer cell motility and invasiveness.
abstract: The viral oncoprotein E7 from the "high-risk" Human Papillomavirus 16 (HPV16) strain is able, when expressed in human keratinocytes, to physically interact with the actin severing protein gelsolin (GSN). In a previous work it has been suggested that this protein-protein interaction can hinder GSN severing function, thus leading to actin network remodeling. In the present work we investigated the possible implications of this molecular interaction in cancer cell metastatic potential by analyzing two different human CC cell lines characterized by low or high expression levels of HPV16 DNA (SiHa and CaSki, respectively). In addition, a HPV-null CC cell line (C-33A), transfected in order to express the HPV16 E7 oncoprotein as well as two different deletion mutants, was also analyzed. We found that HPV16 E7 expression level was directly related with cervical cancer migration and invasion capabilities and that these HPV16 E7-related features were associated with Epithelial to Mesenchymal Transition (EMT) processes. These effects appeared as strictly attributable to the physical interaction of HPV16 E7 with GSN, since HPV16 E7 deletion mutants unable to bind to GSN were also unable to modify microfilament assembly dynamics and, therefore, cell movements and invasiveness. Altogether, these data profile the importance of the physical interaction between HPV16 E7 and GSN in the acquisition of the metastatic phenotype by CC cells, underscoring the role of HPV16 intracellular load as a risk factor in cancer.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Matarrese
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Unit of Cellular Networks and Therapeutic Targets, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Abbruzzese
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Unit of Immunology and Immunotherapy, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mileo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Vona
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ascione
authors.affiliation: Unit of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.affiliation: Unit of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rollo
authors.affiliation: Unit of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.|Istituto San Raffaele Pisana, Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Unit of Cellular Networks and Therapeutic Targets, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Paggi
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D018260:Gelsolin / Q000378:metabolism*; D052162:Human papillomavirus 16; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
chemical_list: D018260:Gelsolin; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: actin; cancer; cell migration; gelsolin; human papillomavirus 16 E7