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PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior and Kills Glioblastoma Stem-like Cells
- Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy.
Author: | Carolin Seifert, Ellen Balz, Susann Herzog, Anna Korolev, Sebastian Gaßmann, Heiko Paland, Matthias A. Fink, Markus Grube, Sascha Marx, Gabriele Jedlitschky, Mladen V. TzvetkovORCiD, Bernhard H. Rauch, Henry W. S. Schroeder, Sandra Bien-Möller |
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URN: | urn:nbn:de:gbv:9-opus-64512 |
DOI: | https://doi.org/10.3390/ijms222011126 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Editor: | Jaroslaw Maciaczyk, Hugo Guerrero-Cazares, Amit Sharma |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2021/10/15 |
Release Date: | 2022/11/18 |
Tag: | PIM1 kinase; glioblastoma; neurospheres; stem-like cells |
GND Keyword: | - |
Volume: | 22 |
Issue: | 20 |
Page Number: | 21 |
Faculties: | Universitätsmedizin / Institut für Pharmakologie |
Licence (German): | Creative Commons - Namensnennung |