Dematin inhibits glioblastoma malignancy through RhoA-mediated CDKs downregulation and cytoskeleton remodeling.
Exp Cell Res
; 417(1): 113196, 2022 08 01.
Article
em En
| MEDLINE
| ID: mdl-35561787
ABSTRACT
Glioblastoma multiforme (GBM) is well known as a highly aggressive brain tumor subtype. Here, we show that overexpression (OE) of dematin actin-binding protein (DMTN) inhibits GBM proliferation and invasion by affecting cell cycle regulation and actin remodeling, respectively. RT-qPCR, western blotting, and immunohistochemical (IHC) staining demonstrated a significant reduction in DMTN expression in gliomas, especially in high-grade gliomas (HGG) compared with normal brains, which correlates with worse survival in HGG patients. Functional studies revealed inhibitory effects of DMTN on tumor proliferation and migratory capacities. The attenuation in tumor proliferative ability upon DMTN OE was accompanied by RhoA suppression and CDK1, CDK2, CDK4, and cyclin D1 downregulation, while RhoA rescue restored the proliferative phenotype. Meanwhile, overexpression of DMTN produced profoundly disorganized stress fibers, which led to impaired tumor invasion. Furthermore, DMTN overexpression produced substantial suppression of tumor growth upon subcutaneous and intracranial implantation in mice, and this was accompanied by significantly reduced vinculin expression and Ki67 positivity. Taken together, these findings demonstrate the role of DMTN in regulating GBM cell proliferation, actin cytoskeleton, and cell morphology and identify DMTN as a vital tumor suppressor in GBM progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto de Actina
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Neoplasias Encefálicas
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Glioblastoma
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Proteínas dos Microfilamentos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article