CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression
Nerve/glial antigen (NG)2 expression crucially determines the aggressiveness of glioblastoma multiforme (GBM). Recent evidence suggests that protein kinase CK2 regulates NG2 expression. Therefore, we investigated in the present study whether CK2 inhibition suppresses proliferation and migration of N...
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MDPI AG
2021-04-01
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| author | Beate M. Schmitt Anne S. Boewe Claudia Götz Stephan E. Philipp Steffi Urbschat Joachim Oertel Michael D. Menger Matthias W. Laschke Emmanuel Ampofo |
| author_facet | Beate M. Schmitt Anne S. Boewe Claudia Götz Stephan E. Philipp Steffi Urbschat Joachim Oertel Michael D. Menger Matthias W. Laschke Emmanuel Ampofo |
| author_sort | Beate M. Schmitt |
| collection | DOAJ |
| description | Nerve/glial antigen (NG)2 expression crucially determines the aggressiveness of glioblastoma multiforme (GBM). Recent evidence suggests that protein kinase CK2 regulates NG2 expression. Therefore, we investigated in the present study whether CK2 inhibition suppresses proliferation and migration of NG2-positive GBM cells. For this purpose, CK2 activity was suppressed in the NG2-positive cell lines A1207 and U87 by the pharmacological inhibitor CX-4945 and CRISPR/Cas9-mediated knockout of CK2α. As shown by quantitative real-time PCR, luciferase-reporter assays, flow cytometry and western blot, this significantly reduced NG2 gene and protein expression when compared to vehicle-treated and wild type controls. In addition, CK2 inhibition markedly reduced NG2-dependent A1207 and U87 cell proliferation and migration. The Cancer Genome Atlas (TCGA)-based data further revealed not only a high expression of both NG2 and CK2 in GBM but also a positive correlation between the mRNA expression of the two proteins. Finally, we verified a decreased NG2 expression after CX-4945 treatment in patient-derived GBM cells. These findings indicate that the inhibition of CK2 represents a promising approach to suppress the aggressive molecular signature of NG2-positive GBM cells. Therefore, CX-4945 may be a suitable drug for the future treatment of NG2-positive GBM. |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:39:22Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-26bea17c99cf4ee1bf7bc9f00cb1bfee2023-11-21T13:58:46ZengMDPI AGCancers2072-66942021-04-01137167810.3390/cancers13071678CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 ExpressionBeate M. Schmitt0Anne S. Boewe1Claudia Götz2Stephan E. Philipp3Steffi Urbschat4Joachim Oertel5Michael D. Menger6Matthias W. Laschke7Emmanuel Ampofo8Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, GermanyMedical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, GermanyExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, GermanyNerve/glial antigen (NG)2 expression crucially determines the aggressiveness of glioblastoma multiforme (GBM). Recent evidence suggests that protein kinase CK2 regulates NG2 expression. Therefore, we investigated in the present study whether CK2 inhibition suppresses proliferation and migration of NG2-positive GBM cells. For this purpose, CK2 activity was suppressed in the NG2-positive cell lines A1207 and U87 by the pharmacological inhibitor CX-4945 and CRISPR/Cas9-mediated knockout of CK2α. As shown by quantitative real-time PCR, luciferase-reporter assays, flow cytometry and western blot, this significantly reduced NG2 gene and protein expression when compared to vehicle-treated and wild type controls. In addition, CK2 inhibition markedly reduced NG2-dependent A1207 and U87 cell proliferation and migration. The Cancer Genome Atlas (TCGA)-based data further revealed not only a high expression of both NG2 and CK2 in GBM but also a positive correlation between the mRNA expression of the two proteins. Finally, we verified a decreased NG2 expression after CX-4945 treatment in patient-derived GBM cells. These findings indicate that the inhibition of CK2 represents a promising approach to suppress the aggressive molecular signature of NG2-positive GBM cells. Therefore, CX-4945 may be a suitable drug for the future treatment of NG2-positive GBM.https://www.mdpi.com/2072-6694/13/7/1678glioblastoma multiformeGBMnerve/glial antigen 2NG2CK2CX-4945 |
| spellingShingle | Beate M. Schmitt Anne S. Boewe Claudia Götz Stephan E. Philipp Steffi Urbschat Joachim Oertel Michael D. Menger Matthias W. Laschke Emmanuel Ampofo CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression Cancers glioblastoma multiforme GBM nerve/glial antigen 2 NG2 CK2 CX-4945 |
| title | CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression |
| title_full | CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression |
| title_fullStr | CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression |
| title_full_unstemmed | CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression |
| title_short | CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression |
| title_sort | ck2 activity mediates the aggressive molecular signature of glioblastoma multiforme by inducing nerve glial antigen ng 2 expression |
| topic | glioblastoma multiforme GBM nerve/glial antigen 2 NG2 CK2 CX-4945 |
| url | https://www.mdpi.com/2072-6694/13/7/1678 |
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