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Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway

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Abstract

A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and remodeling chromatin. In addition to histone acetyltransferase activity, Tip60 is known to regulate a variety of cellular functions, including gene expression, DNA damage response, cell migration and apoptosis. Lower expression of Tip60 is observed in lymphomas, melanomas, breast, colon, and lung cancer. It is widely accepted that Tip60 functions as a tumor suppressor. However, a role of Tip60 in gliomas still remains unclear. In this study, we investigated the role of Tip60 in the malignant behavior of human gliomas. By quantitative RT-PCR analysis using fresh human brain tumor tissues from 55 patients, we found that lower Tip60 expression and higher membrane-type 1 matrix metalloproteinase (MT1-MMP) expression are associated with advanced tumor grade in glioma tissues. Knockdown of Tip60 in glioblastoma cells promoted cell adhesion, spreading and MT1-MMP transcription and thereby invasion, which was suppressed by inhibition of MT1-MMP and nuclear factor-kappa B (NF-κB) activity. We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells by suppressing NF-κB pathway.

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Abbreviations

ECM:

Extracellular matrix

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

MT1-MMP:

Membrane-type 1 matrix metalloproteinase

NF-κB:

Nuclear factor-kappa B

PBS:

Phosphate-buffered saline

QRT-PCR:

Quantitative real-time-PCR

Tip60:

Tat-interacting protein 60 kDa

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Acknowledgments

This work was supported by a KAKENHI Grant from the Japan Society for the Promotion of Science (JSPS)-Japan (Grant No. 23590356 and 25460382).

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Authors and Affiliations

  1. Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan

    Takahisa Takino, Zichen Li, Taisuke Yoshimoto, Takahiro Domoto & Hiroshi Sato

  2. Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan

    Mitsutoshi Nakada

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  1. Takahisa Takino
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  2. Mitsutoshi Nakada
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  3. Zichen Li
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  4. Taisuke Yoshimoto
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  6. Hiroshi Sato
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Correspondence to Takahisa Takino or Hiroshi Sato.

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Takino, T., Nakada, M., Li, Z. et al. Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway. Clin Exp Metastasis 33, 45–52 (2016). https://doi.org/10.1007/s10585-015-9756-8

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  • DOI: https://doi.org/10.1007/s10585-015-9756-8

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