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A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

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Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway
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Norwegian Stem Cell Center, Oslo University Hospital, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
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Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
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Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway
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Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 OSLO, Norway
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Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, P.O. Box 49534 Nydalen, 0424 Oslo, Norway
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Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, P.O. Box 49534 Nydalen, 0424 Oslo, Norway
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Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
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Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1630; https://doi.org/10.3390/cancers12061630
Received: 31 May 2020 / Revised: 13 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. Four primary GSC cultures and two primary adult neural stem cell cultures were treated with G007-LK and subsequently evaluated through the measurement of growth characteristics, as well as the expression of WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Treatment with G007-LK decreased in vitro proliferation and sphere formation in all four primary GSC cultures in a dose-dependent manner. G007-LK treatment altered the expression of key downstream WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Finally, cotreatment with the established GBM chemotherapeutic compound temozolomide (TMZ) led to an additive reduction in sphere formation, suggesting that WNT/β-catenin signaling may contribute to TMZ resistance. These observations suggest that tankyrase inhibition may serve as a supplement to current GBM therapy, although more work is needed to determine the exact downstream mechanisms involved. View Full-Text
Keywords: glioblastoma; glioma stem cells; tankyrase; temozolomide; β-catenin; WNT; Hippo glioblastoma; glioma stem cells; tankyrase; temozolomide; β-catenin; WNT; Hippo
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Kierulf-Vieira, K.S.; Sandberg, C.J.; Waaler, J.; Lund, K.; Skaga, E.; Saberniak, B.M.; Panagopoulos, I.; Brandal, P.; Krauss, S.; Langmoen, I.A.; Vik-Mo, E.O. A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation. Cancers 2020, 12, 1630.

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