Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion
Glioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in gliobla...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/14/1/89 |
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| author | Sarah F. Stuart Peter Curpen Adele J. Gomes Michelle C. Lan Shuai Nie Nicholas A. Williamson George Kannourakis Andrew P. Morokoff Adrian A. Achuthan Rodney B. Luwor |
| author_facet | Sarah F. Stuart Peter Curpen Adele J. Gomes Michelle C. Lan Shuai Nie Nicholas A. Williamson George Kannourakis Andrew P. Morokoff Adrian A. Achuthan Rodney B. Luwor |
| author_sort | Sarah F. Stuart |
| collection | DOAJ |
| description | Glioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma proliferation, epithelial to mesenchymal transition, and invasion. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients using TCGA datasets. Proteomic analysis of glioblastoma cell lines overexpressing IL-11Rα displayed a proteome that favoured enhanced proliferation and invasion. These cells also displayed greater proliferation and migration, while the knockdown of IL-11Rα reversed these tumourigenic characteristics. In addition, these IL-11Rα overexpressing cells displayed enhanced invasion in transwell invasion assays and in 3D spheroid invasion assays, while knockdown of IL-11Rα resulted in reduced invasion. Furthermore, IL-11Rα-overexpressing cells displayed a more mesenchymal-like phenotype compared to parental cells and expressed greater levels of the mesenchymal marker Vimentin. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell proliferation, EMT, and invasion. |
| first_indexed | 2024-03-08T11:03:17Z |
| format | Article |
| id | doaj.art-67b463ca5fd74a849d24bbbf4752968b |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-08T11:03:17Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-67b463ca5fd74a849d24bbbf4752968b2024-01-26T15:25:14ZengMDPI AGBrain Sciences2076-34252024-01-011418910.3390/brainsci14010089Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and InvasionSarah F. Stuart0Peter Curpen1Adele J. Gomes2Michelle C. Lan3Shuai Nie4Nicholas A. Williamson5George Kannourakis6Andrew P. Morokoff7Adrian A. Achuthan8Rodney B. Luwor9Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaTownsville Hospital and Health Service, James Cook University, Townsville, QLD 4814, AustraliaDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaMelbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3052, AustraliaMelbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3052, AustraliaFiona Elsey Cancer Research Institute, Ballarat, VIC 3350, AustraliaDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaDepartment of Medicine, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, AustraliaGlioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma proliferation, epithelial to mesenchymal transition, and invasion. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients using TCGA datasets. Proteomic analysis of glioblastoma cell lines overexpressing IL-11Rα displayed a proteome that favoured enhanced proliferation and invasion. These cells also displayed greater proliferation and migration, while the knockdown of IL-11Rα reversed these tumourigenic characteristics. In addition, these IL-11Rα overexpressing cells displayed enhanced invasion in transwell invasion assays and in 3D spheroid invasion assays, while knockdown of IL-11Rα resulted in reduced invasion. Furthermore, IL-11Rα-overexpressing cells displayed a more mesenchymal-like phenotype compared to parental cells and expressed greater levels of the mesenchymal marker Vimentin. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell proliferation, EMT, and invasion.https://www.mdpi.com/2076-3425/14/1/89interleukin 11glioblastomaEMTinvasion |
| spellingShingle | Sarah F. Stuart Peter Curpen Adele J. Gomes Michelle C. Lan Shuai Nie Nicholas A. Williamson George Kannourakis Andrew P. Morokoff Adrian A. Achuthan Rodney B. Luwor Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion Brain Sciences interleukin 11 glioblastoma EMT invasion |
| title | Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion |
| title_full | Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion |
| title_fullStr | Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion |
| title_full_unstemmed | Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion |
| title_short | Interleukin-11/IL-11 Receptor Promotes Glioblastoma Cell Proliferation, Epithelial–Mesenchymal Transition, and Invasion |
| title_sort | interleukin 11 il 11 receptor promotes glioblastoma cell proliferation epithelial mesenchymal transition and invasion |
| topic | interleukin 11 glioblastoma EMT invasion |
| url | https://www.mdpi.com/2076-3425/14/1/89 |
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