TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway.
Oncol Rep
; 41(2): 753-764, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30431125
ABSTRACT
Trophoblast cell surface antigen 2 (TROP2), a single transmembrane domain protein, is often found to be highly expressed in various types of human cancers. However, the biological function and molecular mechanism of TROP2 in glioblastoma have not been fully elucidated, particularly in regards to cell proliferation and metastasis of glioblastoma cells. In the present study, it was demonstrated that TROP2 expression was increased in glioblastoma tissues and glioblastoma cell lines by immunohistochemical analysis and western blot analysis. High TROP2 expression was significantly correlated with the poor survival of glioblastoma patients. MTT assay, BrdU incorporation assay, flow cytometry and Transwell assay were performed to demonstrate that knockdown of TROP2 in glioblastoma cells inhibited cell proliferation and metastasis. We found that the effects of TROP2knockdown on glioblastoma cells were associated with the inhibition of JAK2 and STAT3 phosphorylation and decreased transcription of STAT3 target genes. In addition, blocking the activation of JAK2/STAT3 signaling by WP1066 negated the effects of TROP2 overexpression. Furthermore, exogenous IL6, which functions as a potent activator of JAK2/STAT3 signaling, was able to rescue the phosphorylation of JAK2 and STAT3 in TROP2silenced glioblastoma cells and regulate phenotypic changes in these cells. Therefore, we revealed a novel mechanism by which TROP2 activates the JAK2/STAT3 pathway to promote the growth and metastasis of glioblastoma cells. These data offer insight into the function of TROP2 in glioblastoma and indicate that TROP2 is a promising biomarker and therapeutic target for glioblastoma patients.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Biomarcadores Tumorais
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Moléculas de Adesão Celular
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Glioblastoma
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Antígenos de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Aged80
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article