The Asian-American variant of human papillomavirus type 16 exhibits higher activation of MAPK and PI3K/AKT signaling pathways, transformation, migration and invasion of primary human keratinocytes

Autor(es)

Hochmann, Jimena ^[1] ; Sobrinho, Joao S. ^[1] ; Villa, Luisa L. ^{[1, 2]} ; Sichero, Laura ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Ctr Translat Res Oncol, Inst Canc Estado Sao Paulo, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Radiol & Oncol, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: VIROLOGY; v. 492, p. 145-154, MAY 2016.
• Citações Web of Science: 6

Resumo

Asian-American (AA) HPV-16 variants are associated with higher risk of cancer. Abnormal activation of intracellular signaling play a critical role in cancer development and progression. Our aim was to elucidate mechanisms underlying the higher oncogenic potential attributed to AA variant. We evaluated activation of MAPK and PI3K/AKT pathways in primary human keratinocytes (PHKs) transduced with E6/E7 of three HPV-16 variants: E-P, AA, E-350G. Phenotypes examined included migration, anchorage independent growth and invasion. AA PHKs presented the highest levels of active proteins involved in all cascades analyzed: MAPK-ERK, MAPK-p38 and PI3K-AKT. AA PHKs were more efficient in promoting anchorage independent growth, and in stimulating cell migration and invasion. MEK1 inhibition decreased migration. The mesenchymal phenotype marker vimentin was increased in AA PHKs. Our results suggest that MEK1, ERK2, AKT2 hyperactivation influence cellular behavior by means of GSK-3b inactivation and EMT induction prompting AA immortalized PHKs to more efficiently surpass carcinogenesis steps. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 12/16283-9 - Análise do impacto das proteínas E6/E7 de diferentes variantes moleculares de HPV-16 sob as vias de transdução de sinal mediadas por MAPK
• Beneficiário: Laura Cristina Sichero Vettorazzo
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/57889-1 - Instituto de Ciência e Tecnologia para o Estudo das Doenças Associadas ao Papilomavírus
• Beneficiário: Luisa Lina Villa
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/01538-4 - Análise do impacto das proteínas E6/E7 de diferentes variantes moleculares de HPV-16 sob as vias de transdução de sinal mediadas por MAPK
• Beneficiário: Jimena Paola Hochmann Valls
• Linha de fomento: Bolsas no Brasil - Doutorado