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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Hochmann, Jimena [1] ; Sobrinho, Joao S. [1] ; Villa, Luisa L. [1, 2] ; Sichero, Laura [1]
Total Authors: 4
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: VIROLOGY; v. 492, p. 145-154, MAY 2016.
Web of Science Citations: 6
Abstract

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)

FAPESP's process: 08/57889-1 - Institute of Science and Technology to study Diseases Associated with Papillomavirus
Grantee:Luisa Lina Villa
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/16283-9 - Analysis of the impact of E6/E7 proteins of different HPV-16 molecular variants upon signal transduction pathways mediated by MAPK
Grantee:Laura Cristina Sichero Vettorazzo
Support type: Regular Research Grants
FAPESP's process: 13/01538-4 - Análisis of the impact of E6/E7 proteins of different HPV16 molecular variants upon signal transduction pathways mediated by MAPK
Grantee:Jimena Paola Hochmann Valls
Support type: Scholarships in Brazil - Doctorate