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Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells

Cancer Gene Therapy volume 18, pages 206–218 (2011)Cite this article

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Abstract

We have previously reported the presence of Dlxin-1, a member of the melanoma antigen gene (MAGE) family, in the brain and showed its function as a cell cycle arrest protein, suggesting that Dlxin-1 may have anti-proliferative functions in rapidly growing tumors. Using the cancer stem cell hypothesis, which attributes the initiation and progression of brain tumors to the cancer-initiating stem cells, we have investigated the role of Dlxin-1 in the glioma stem cells propagated by us as a cell culture system comprising of HNGC-2 cells. Our studies provide evidence about the role of Dlxin-1 as an anti-tumorigenic protein in the highly chemo-resistant glioma stem cells. Next, we show that these anti-proliferative effects are manifested by Dlxin-1 through down regulation of the activities of MMP-2 and MMP-9, and through interaction of Dlxin-1 with its target protein P311 that is involved in glioma cell invasion. In summary, we establish the roles for Dlxin-1, one as an anti-tumorigenic and anti-invasive protein in high-grade gliomas and the other as an inducer of differentiation of glioma stem cells. These two attributes, in conjunction, result in conversion of the drug-resistant brain tumor stem cells to the tumor-attenuated cells that may now be more amenable to effective therapeutic targeting.

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Acknowledgements

We sincerely thank Dr Dattatraya Mujumdar, KEM Hospital, Mumbai for providing us with glioma samples, Dr Mahesh M Mandolkar, Dinanath Mangeshkar Hospital, Pune for the histopathology sections, CSIR, Government of India for student fellowships and NCCS, Pune, India for intramural financial support and DBT, Government of India for extra-mural funding support for the research work.

Grant: Grant support provided by Department of Biotechnology, Government of India, New Delhi. The fellowship of EMR, STC, RGK and NK was supported by Council of Scientific and Industrial Research (CSIR), New Delhi, India.

Disclaimer

The manuscript entitled ‘Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells’ is original research.

The above mentioned submitted manuscript has not been previously published.

We have not sent this manuscript for publication elsewhere while it is under consideration in Cancer Gene Therapy.

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  1. E M Reddy and S T Chettiar: These authors contributed equally this work.

Authors and Affiliations

  1. National Centre for Cell Science (NCCS), NCCS Complex, University of Pune Campus, Pune, Maharashtra, India

    E M Reddy, S T Chettiar, N Kaur, R Ganeshkumar, V Shepal, N C Shanbhag & A Shiras

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  1. E M Reddy
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Correspondence to A Shiras.

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Reddy, E., Chettiar, S., Kaur, N. et al. Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells. Cancer Gene Ther 18, 206–218 (2011). https://doi.org/10.1038/cgt.2010.71

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