The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis
- Author(s)
- Stuart, SF; Bezawork-Geleta, A; Areeb, Z; Gomez, J; Tsui, V; Zulkifli, A; Paradiso, L; Jones, J; Nguyen, HPT; Putoczki, TL; Licciardi, PV; Kannourakis, G; Morokoff, AP; Achuthan, AA; Luwor, RB;
- Details
- Publication Year 2023-02-08,Volume 24,Issue #4,Page 3356
- Journal Title
- International Journal of Molecular Sciences
- Abstract
- Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.
- Publisher
- MDPI
- Keywords
- Humans; Cell Line; Cell Line, Tumor; *Glioblastoma/metabolism; Glucose/metabolism; Interleukin-11/metabolism; Receptors, Interleukin-11; Il-11; glioblastoma; glutaminolysis; invasion; survival
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 36834778
- Publisher's Version
- https://doi.org/10.3390/ijms24043356
- Open Access at Publisher's Site
https://doi.org/10.3390/ijms24043356- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-08 03:16:07
Last Modified: 2023-03-08 04:07:15