Proteases and HPV-Induced Carcinogenesis

Autor(es)

Vieira, Gabriel Viliod ; Somera dos Santos, Fernanda ; Lepique, Ana Paula ; da Fonseca, Carol Kobori ; Innocentini, Lara Maria Alencar Ramos ; Braz-Silva, Paulo Henrique ; Quintana, Silvana Maria ; Sales, Katiuchia Uzzun

• Tipo de documento: Artigo Científico
• Fonte: CANCERS; v. 14, n. 13, p. 25-pg., 2022-07-01.

Resumo

Simple Summary Human papillomavirus (HPV) infection is a sexually transmitted disease with high prevalence worldwide. Although most HPV infections do not lead to cancer, some HPV types are correlated with the majority of cervical cancers, and with some anogenital and oropharyngeal cancers. Moreover, enzymes known as proteases play an essential role in the pathogenic process in HPV-induced carcinogenesis. This review highlights the role of proteases and recent epidemiological data regarding HPV-dependent carcinogenesis. Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival. (AU)

• Processo FAPESP: 14/06316-2 - Estudo genético da via proteolítica da matriptase em câncer de cabeça e pescoço
• Beneficiário: Katiuchia Uzzun Sales
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/04896-5 - Modulação do perfil proteolítico em pacientes com lesões intraepiteliais de alto grau do colo uterino e em linhagem celular de carcinoma de colo de útero
• Beneficiário: Katiuchia Uzzun Sales
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/16989-5 - O microambiente tumoral e a modulação da resposta de células mielóides.
• Beneficiário: Ana Paula Lepique
• Modalidade de apoio: Auxílio à Pesquisa - Regular