title: The NFκB Signaling Pathway in Papillomavirus-induced Lesions: Friend or Foe?
abstract: Papillomaviruses induce a range of benign and malignant lesions in their hosts, including cervical cancer, that is associated with high-risk human papillomavirus (HPV) types. The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) plays a pivotal role in HPV-infected cells, and its expression and activity are modulated by several viral oncoproteins. NFκB modulation seems to first facilitate viral persistence and immune evasion, and later to drive tumour progression, but the many conflicting results and the complexity of its signaling networks require great prudence while interpreting the role of NFκB in papillomaviral lesions. Accordingly, the pharmacological targeting of the NFκB pathway in HPV-induced lesions is a complex and currently unmet challenge. This review deals with recent findings concerning NFκB activation in HPV-infected cells, its role in viral persistence, cell transformation and tumour progression, and with current efforts to target this pathway for cancer prevention and therapy.
authors.affiliation: Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Chemical Engineering Department, Engineering Faculty, University of Porto, Porto, Portugal Molecular Oncology Group, IPO-Porto Research Centre (CI-IPOP) and Virology Laboratory, Portuguese Oncology Institute, Porto, Portugal.
authors.forename: Rui M Gil
authors.initials: RM
authors.lastname: DA Costa
authors.affiliation: Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Chemical Engineering Department, Engineering Faculty, University of Porto, Porto, Portugal.
authors.forename: Margarida M S M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: Molecular Oncology Group, IPO-Porto Research Centre (CI-IPOP) and Virology Laboratory, Portuguese Oncology Institute, Porto, Portugal Abel Salazar Institute for Biomedical Sciences, University of Porto, Porto, Portugal Biomedicine Research Centre, Health Sciences Faculty, Fernando Pessoa University, Porto, Portugal Research Department, Portuguese League against Cancer, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: Biological and Agroenvironmental Technology Research Centre (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal pamo@utad.pt.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
mesh_terms: D052685:Alphapapillomavirus / Q000472:pathogenicity*; D063646:Carcinogenesis; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B
keywords: Apoptosis; HPV; IKK; NFκB; human papillomavirus; inflammation; review; targeted therapy