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.

The small molecule SI113 hinders epithelial‐to‐mesenchymal transition and subverts cytoskeletal organization in human cancer cells

“…On the bases of these results, and assumed the involvement of this drug in affecting key cellular functions, we sought to assess the ability of SI113 in interfering with cancer cell motility using the following human cancer cell lines: ADF (GBM), HepG2, (HCC), and HCT116 (CRC). These cancer cells were brought to confluence and then subjected to a wound as described (in vitro scratch assay; Liang et al, ; Matarrese et al, ). Cells were then immediately incubated in growth medium in the absence or in the presence of SI113 at concentrations varying between 12.5 and 20 μM according to the different sensitivity of each cell line toward the compound.…”

Inflammatory cytokines associated with cancer growth induce mitochondria and cytoskeleton alterations in cardiomyocytes

“…Cells were fixed with 4% paraformaldehyde and then permeabilized by 0.5% (vol/vol) Triton X-100 as reported (Matarrese et al, 2016)…”

Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand

“…GSN is an evolutionary highly conserved protein in vertebrates and exists in four isoforms. cGSN has multifunctional roles in various physiological and pathological processes such as regulation of actin cytoskeleton dynamics, cell motility, and metastasis [29,30]. Furthermore, cGSN plays critical roles in apoptosis signaling and cell differentiation [31].…”