A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1630 |
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| author | Kirsten Strømme Kierulf-Vieira Cecilie Jonsgar Sandberg Jo Waaler Kaja Lund Erlend Skaga Birthe Mikkelsen Saberniak Ioannis Panagopoulos Petter Brandal Stefan Krauss Iver Arne Langmoen Einar Osland Vik-Mo |
| author_facet | Kirsten Strømme Kierulf-Vieira Cecilie Jonsgar Sandberg Jo Waaler Kaja Lund Erlend Skaga Birthe Mikkelsen Saberniak Ioannis Panagopoulos Petter Brandal Stefan Krauss Iver Arne Langmoen Einar Osland Vik-Mo |
| author_sort | Kirsten Strømme Kierulf-Vieira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:02:40Z |
| format | Article |
| id | doaj.art-e5684aa403ca47329369cac9db4d7ecf |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:02:40Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e5684aa403ca47329369cac9db4d7ecf2023-11-20T04:22:02ZengMDPI AGCancers2072-66942020-06-01126163010.3390/cancers12061630A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere FormationKirsten Strømme Kierulf-Vieira0Cecilie Jonsgar Sandberg1Jo Waaler2Kaja Lund3Erlend Skaga4Birthe Mikkelsen Saberniak5Ioannis Panagopoulos6Petter Brandal7Stefan Krauss8Iver Arne Langmoen9Einar Osland Vik-Mo10Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayDepartment of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayDepartment of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwaySection for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, P.O. Box 49534 Nydalen, 0424 Oslo, NorwaySection for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, P.O. Box 49534 Nydalen, 0424 Oslo, NorwayDepartment of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayEvidence 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.https://www.mdpi.com/2072-6694/12/6/1630glioblastomaglioma stem cellstankyrasetemozolomideβ-cateninWNT |
| spellingShingle | Kirsten Strømme Kierulf-Vieira Cecilie Jonsgar Sandberg Jo Waaler Kaja Lund Erlend Skaga Birthe Mikkelsen Saberniak Ioannis Panagopoulos Petter Brandal Stefan Krauss Iver Arne Langmoen Einar Osland Vik-Mo A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation Cancers glioblastoma glioma stem cells tankyrase temozolomide β-catenin WNT |
| title | A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation |
| title_full | A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation |
| title_fullStr | A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation |
| title_full_unstemmed | A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation |
| title_short | A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation |
| title_sort | small molecule tankyrase inhibitor reduces glioma stem cell proliferation and sphere formation |
| topic | glioblastoma glioma stem cells tankyrase temozolomide β-catenin WNT |
| url | https://www.mdpi.com/2072-6694/12/6/1630 |
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