Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway.

Neuro-oncology
Ichiro NakanoHarley I Kornblum

Abstract

Glioblastoma multiforme (GBM) is a devastating disease, and the current therapies have only palliative effect. Evidence is mounting to indicate that brain tumor stem cells (BTSCs) are a minority of tumor cells that are responsible for cancer initiation, propagation, and maintenance. Therapies that fail to eradicate BTSCs may ultimately lead to regrowth of residual BTSCs. However, BTSCs are relatively resistant to the current treatments. Development of novel therapeutic strategies that effectively eradicate BTSC are, therefore, essential. In a previous study, we used patient-derived GBM sphere cells (stemlike GBM cells) to enrich for BTSC and identified maternal embryonic leucine-zipper kinase (MELK) as a key regulator of survival of stemlike GBM cells in vitro. Here, we demonstrate that a thiazole antibiotic, siomycin A, potently reduced MELK expression and inhibited tumor growth in vivo. Treatment of stemlike GBM cells with siomycin A resulted in arrested self-renewal, decreased invasion, and induced apoptosis but had little effect on growth of the nonstem cells of matched tumors or normal neural stem/progenitor cells. MELK overexpression partially rescued the phenotype of siomycin A-treated stemlike GBM cells. In vivo, siomyc...Continue Reading

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Citations

Mar 14, 2012·Future Oncology·Yu LiSuyun Huang
Jan 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takeshi MiyazakiIchiro Nakano
Jun 5, 2013·Neuro-oncology·Pierpaolo PeruzziJakub Godlewski
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Mar 5, 2020·Molecular Cancer Therapeutics·Daisuke YamashitaIchiro Nakano
May 6, 2014·Molecular Cancer Therapeutics·Ranjit GangulyIchiro Nakano
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Dec 20, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hacer GuvencIchiro Nakano
Jul 1, 2021·Oncology Letters·Yuying WuXinhua Zhang

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