Abstract
DNA topoisomerase II alpha (TOP2A) reportedly plays a crucial role in several cancers, however, the precise regulatory role of TOP2A in metastatic characteristics of glioma is still poorly understood. Herein, we sought to elucidate the mechanisms by which TOP2A affects the metastatic phenotypes of glioma. We observed that a high level of TOP2A expression was dramatically linked with inferior survival in glioma patients while silencing of TOP2A impaired glioma cell proliferation and aggressiveness. TOP2A was found to directly interact with β-catenin and facilitated its translocation into the nucleus. Mechanistically, TOP2A effectively induced glioma cell growth and invasion in a β-catenin-dependent manner. Overall, we pinpoint TOP2A as a critical activator of the Wnt/β-catenin pathway in glioma, promoting cell growth, migration, and invasion.
Keywords:
MMPs; TOP2A; glioma; invasion; β-catenin.
Publication types
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Cell Line, Tumor
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DNA Topoisomerases, Type II / genetics
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DNA Topoisomerases, Type II / metabolism*
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Gene Expression Regulation, Neoplastic*
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Glioma / genetics
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Glioma / metabolism*
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Glioma / pathology
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Humans
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Neoplasm Metastasis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Poly-ADP-Ribose Binding Proteins / genetics
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Poly-ADP-Ribose Binding Proteins / metabolism*
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Transcriptional Activation*
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beta Catenin / biosynthesis*
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beta Catenin / genetics
Substances
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CTNNB1 protein, human
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Neoplasm Proteins
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Poly-ADP-Ribose Binding Proteins
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beta Catenin
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DNA Topoisomerases, Type II
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TOP2A protein, human
Grants and funding
This study was supported by The Yunnan Provincial High-level Health and Family Planning Technical Talent Training Fund supports the Yunnan Provincial Health Commission’s Medical Reserve Talent Training Program (No. H-2018054).