PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells.

Witte KE, Slotta C, Lütkemeyer M, Kitke A, Coras R, Simonis M, Kaltschmidt C, Kaltschmidt B (2020)
Scientific reports 10(1): 21858.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Witte, Kaya Elisa; Slotta, CarstenUniBi; Lütkemeyer, Melanie; Kitke, Angelika; Coras, Roland; Simonis, MatthiasUniBi; Kaltschmidt, ChristianUniBi; Kaltschmidt, BarbaraUniBi
Abstract / Bemerkung
A signalling pathway involving PLEKHG5 (guanine exchange factor) for the Ras superfamily member RAB26 to transcription factor NF-kappaB was discovered in autophagy. PLEKHG5 was reported in glioblastoma multiforme (GBM) and correlates with patient survival. Thus, the generation of a cellular model for understanding PLEKHG5 signalling is the study purpose. We generated a CRISPR/Cas9-mediated knockout of PLEKHG5 in U251-MG glioblastoma cells and analysed resulting changes. Next, we used a mRFP-GFP-LC3+ reporter for visualisation of autophagic defects and rescued the phenotype of PLEKHG5 wildtype via transduction of a constitutively active RAB26QL-plasmid. Effects of overexpressing RAB26 were investigated and correlated with the O6-methylguanine-DNA methyltransferase (MGMT) and cellular survival. PLEKHG5 knockout showed changes in morphology, loss of filopodia and higher population doubling times. Accumulation of autolysosomes was resulted by decreased LAMP-1 in PLEKHG5-deficient cells. Rescue of PLEKHG5-/- restored the downregulation of RhoA activity, showed faster response to tumour necrosis factor and better cellular fitness. MGMT expression was activated after RAB26 overexpression compared to non-transduced cells. Survival of PLEKHG5 knockout was rescued together with sensitivity to temozolomide by RAB26QL. This study provides new insights in the PLEKHG5/RAB26 signalling within U251-MG cells, which suggests potential therapeutic strategies in other glioma cells and further in primary GBM.
Erscheinungsjahr
2020
Zeitschriftentitel
Scientific reports
Band
10
Ausgabe
1
Art.-Nr.
21858
eISSN
2045-2322
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld im Rahmen des DEAL-Vertrags gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2949988

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Witte KE, Slotta C, Lütkemeyer M, et al. PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells. Scientific reports. 2020;10(1): 21858.
Witte, K. E., Slotta, C., Lütkemeyer, M., Kitke, A., Coras, R., Simonis, M., Kaltschmidt, C., et al. (2020). PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells. Scientific reports, 10(1), 21858. https://doi.org/10.1038/s41598-020-77958-3
Witte, K. E., Slotta, C., Lütkemeyer, M., Kitke, A., Coras, R., Simonis, M., Kaltschmidt, C., and Kaltschmidt, B. (2020). PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells. Scientific reports 10:21858.
Witte, K.E., et al., 2020. PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells. Scientific reports, 10(1): 21858.
K.E. Witte, et al., “PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells.”, Scientific reports, vol. 10, 2020, : 21858.
Witte, K.E., Slotta, C., Lütkemeyer, M., Kitke, A., Coras, R., Simonis, M., Kaltschmidt, C., Kaltschmidt, B.: PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells. Scientific reports. 10, : 21858 (2020).
Witte, Kaya Elisa, Slotta, Carsten, Lütkemeyer, Melanie, Kitke, Angelika, Coras, Roland, Simonis, Matthias, Kaltschmidt, Christian, and Kaltschmidt, Barbara. “PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells.”. Scientific reports 10.1 (2020): 21858.
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2021-01-22T07:27:54Z
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