Nuclear unphosphorylated STAT3 correlates with a worse prognosis in human glioblastoma

Autor(es)

Rodrigues, Bruna R. ^[1] ; Queiroz-Hazarbassanov, Nicolle ^[1] ; Lopes, Marilene H. ^[2] ; Bleggi-Torres, Luis F. ^[3] ; Suzuki, Sergio ^[4] ; Cunha, Isabela W. ^[5] ; Sanematsu, Paulo ^[4] ; Martins, Vilma R. ^[1]

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Int Res Ctr, Rua Tagua 440, BR-01508010 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Ave Prof Lineu Prestes 1524, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Parana, Dept Pathol, Rua Padre Camargo 280, BR-80060240 Curitiba, Parana - Brazil

^[4] AC Camargo Canc Ctr, Dept Neurosurg, Rua Antonio Prudente 211, BR-01509010 Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Dept Pathol, Rua Antonio Prudente 211, BR-01509010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PATHOLOGY RESEARCH AND PRACTICE; v. 212, n. 6, p. 517-523, 2016.
• Citações Web of Science: 5

Resumo

Glioblastoma (GBM) is currently the most aggressive form of brain tumor identified, and STAT3 is known to play an important role in gliomagenesis. Moreover, while several studies have used pharmacological approaches to modulate STAT3 activity, the results have been contradictory. In this study, expressions of STAT3, pSTAT3 (Y705), and pSTAT3 (S727) were evaluated using immunohistochemistry assays of tissue microarrays containing non-neoplastic tissue (NN, n = 12), grade II astrocytomas (n = 33), grade III astrocytomas (n = 12), and GBM (n = 85) specimens. In GBM specimens, STAT3 was overexpressed and exhibited greater nuclear localization compared with lower grade astrocytomas and NN. Conversely, nuclear localization of pSTAT3 (Y705) and pSTAT3 (S727) exhibited a similar phenotype in both GBMs and NNs. MET was also detected as a non-canonical pathway marker for STAT3. For tumors with higher levels of STAT3 nuclear localization, and not pSTAT3 (Y705) and pSTAT3 (S727), these specimens exhibited increased levels of MET expression. Thus, a non-canonical pathway may mediate a proportion of the STAT3 that translocates to the nucleus. Moreover, tumors which exhibited greater nuclear localization of STAT3 corresponded with patients that presented with lower rates of recurrence-free survival and overall survival. In contrast, the phosphorylated forms of STAT3 did not correlate with patient survival. These findings suggest that phosphorylation-independent mechanisms may mediate the nuclear translocation and activation of STAT3. Further studies are needed to identify the mechanisms involved, especially those that provide targets to achieve efficient inhibition and control of GBM progression. (C) 2016 Elsevier GmbH. All rights reserved. (AU)

• Processo FAPESP: 09/51751-0 - Estudo funcional da expressão de STI1/Hop e proteínas da cascata de sumoilação em gliomas: correlação com proliferação celular e características clínico-patológicas
• Beneficiário: Nicolle Gilda Teixeira de Queiroz
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/13654-0 - Regulação da atividade de STAT3 por STI1/Hop em glioblastoma.
• Beneficiário: Bruna Roz Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/14027-2 - Mecanismos associados à função da proteína prion e seu ligante STI1/Hop: abordagens terapêuticas
• Beneficiário: Vilma Regina Martins
• Modalidade de apoio: Auxílio à Pesquisa - Temático