A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation
by
Kirsten Strømme Kierulf-Vieira 1,2,3,*
, Cecilie Jonsgar Sandberg 1,2, Jo Waaler 4,5, Kaja Lund 4,5, Erlend Skaga 1,2,3, Birthe Mikkelsen Saberniak 1,2, Ioannis Panagopoulos 6, Petter Brandal 6,7,8, Stefan Krauss 4,5, Iver Arne Langmoen 1,2,3,8,9 and Einar Osland Vik-Mo 1,2,3,8,9
Kirsten Strømme Kierulf-Vieira 1,2,3,*, Cecilie Jonsgar Sandberg 1,2, Jo Waaler 4,5, Kaja Lund 4,5, Erlend Skaga 1,2,3, Birthe Mikkelsen Saberniak 1,2, Ioannis Panagopoulos 6, Petter Brandal 6,7,8, Stefan Krauss 4,5, Iver Arne Langmoen 1,2,3,8,9 and Einar Osland Vik-Mo 1,2,3,8,9
1
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
2
Norwegian Stem Cell Center, Oslo University Hospital, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
3
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
4
Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, Norway
5
Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 OSLO, Norway
6
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
7
Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, P.O. Box 49534 Nydalen, 0424 Oslo, Norway
8
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway
9
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.
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Keywords:
glioblastoma; glioma stem cells; tankyrase; temozolomide; β-catenin; WNT; Hippo
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MDPI and ACS Style
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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