Interaction between the human papillomavirus 16 E7 oncoprotein and gelsolin ignites cancer cell motility and invasiveness

Paola Matarrese, Claudia Abbruzzese, Anna Maria Mileo, Rosa Vona, Barbara Ascione, Paolo Visca, Francesca Rollo, Maria Benevolo, Walter Malorni, Marco G. Paggi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)50972-50985
Number of pages14
JournalOncotarget
Volume7
Issue number32
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Actin
  • Cancer
  • Cell migration
  • Gelsolin
  • Human papillomavirus 16 E7

ASJC Scopus subject areas

  • Oncology

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