Pololike kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma.
Oncol Rep
; 41(4): 2159-2167, 2019 Apr.
Article
en En
| MEDLINE
| ID: mdl-30816483
ABSTRACT
Glioblastoma (GBM) is one of the most malignant tumors in adults, associated with severe outcomes (median survival, <2 years). Multiple mechanisms are known to be involved in tumor recurrence and treatment resistance in GBM, however, the key regulator for GBM tumorigenesis and therapy resistance remains unclear. To clarify a novel potential functional mechanism of GBM recurrence, a wide range of experiments including in vitro molecular biological experiments and in vivo intracranial xenograft tumor models were performed in the present study. With bioinformatics analysis, pololike kinase 4 (PLK4) was initially identified as one of the most upregulated kinase encoding genes in GBM, which was functionally required for both in vitro cell proliferation and in vivo tumorigenesis in GBM. Clinically, an elevated PLK4 expression was observed in high grade glioma patients, which was associated with poor prognosis. In addition, PLK4 enhanced radioresistance in GBM, while PLK4 knockdown via lentivirus transfection significantly increased the radiosensitivity of GBM cells. Mechanically, PLK4 expression was markedly elevated by the exogenous overexpression of ATPase family AAA domaincontaining protein 2 (ATAD2) in GBM cells. Collectively, the results suggested that the ATAD2dependent transcriptional regulation of PLK4 promoted cell proliferation and tumorigenesis, as well as radioresistance in GBM, thus potentially inducing tumor recurrence. PLK4 could therefore serve as a potential therapeutic target for GBM treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tolerancia a Radiación
/
Neoplasias Encefálicas
/
Proteínas Serina-Treonina Quinasas
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Glioblastoma
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Proteínas de Unión al ADN
/
ATPasas Asociadas con Actividades Celulares Diversas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article