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Article

Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function

1
Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea
2
Department of Neurosurgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea
3
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea
4
Department of Biological Sciences, Pusan National University, Busan 46241, Korea
*
Authors to whom correspondence should be addressed.
Current affiliation: Institute of Bioinnovation Research, Kolon Life Science, Seoul 07793, Korea.
Academic Editor: Giuseppe Lombardi
Int. J. Mol. Sci. 2021, 22(6), 2982; https://doi.org/10.3390/ijms22062982
Received: 15 February 2021 / Revised: 8 March 2021 / Accepted: 12 March 2021 / Published: 15 March 2021
(This article belongs to the Special Issue The Molecular Basis of Therapeutic Resistance of Brain Tumor)
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with poor patient prognosis. Although the standard treatment of GBM is surgery followed by chemotherapy and radiotherapy, often a small portion of surviving tumor cells acquire therapeutic resistance and become more aggressive. Recently, altered kinase expression and activity have been shown to determine metabolic flux in tumor cells and metabolic reprogramming has emerged as a tumor progression regulatory mechanism. Here we investigated novel kinase-mediated metabolic alterations that lead to acquired GBM radioresistance and malignancy. We utilized transcriptomic analyses within a radioresistant GBM orthotopic xenograft mouse model that overexpresses the dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3). We find that within GBM cells, radiation exposure induces DYRK3 expression and DYRK3 regulates mammalian target of rapamycin complex 1 (mTORC1) activity through phosphorylation of proline-rich AKT1 substrate 1 (PRAS40). We also find that DYRK3 knockdown inhibits dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, leading to increased oxidative phosphorylation (OXPHOS) and reduced glycolysis. Importantly, enforced DYRK3 downregulation following irradiation significantly impaired GBM cell migration and invasion. Collectively, we suggest DYRK3 suppression may be a novel strategy for preventing GBM malignancy through regulating mitochondrial metabolism. View Full-Text
Keywords: DYRK3; glioblastoma multiforme; radioresistance; mitochondrial fission DYRK3; glioblastoma multiforme; radioresistance; mitochondrial fission
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MDPI and ACS Style

Kim, K.; Lee, S.; Kang, H.; Shin, E.; Kim, H.Y.; Youn, H.; Youn, B. Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function. Int. J. Mol. Sci. 2021, 22, 2982. https://doi.org/10.3390/ijms22062982

AMA Style

Kim K, Lee S, Kang H, Shin E, Kim HY, Youn H, Youn B. Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function. International Journal of Molecular Sciences. 2021; 22(6):2982. https://doi.org/10.3390/ijms22062982

Chicago/Turabian Style

Kim, Kyeongmin, Sungmin Lee, Hyunkoo Kang, Eunguk Shin, Hae Y. Kim, HyeSook Youn, and BuHyun Youn. 2021. "Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function" International Journal of Molecular Sciences 22, no. 6: 2982. https://doi.org/10.3390/ijms22062982

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