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https://doi.org/10.1038/s41467-017-01392-9
| Title: | Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme | Authors: | Newman J.P. Wang G.Y. Arima K. Guan S.P. Waters M.R. Cavenee W.K. Pan E. Aliwarga E. Chong S.T. Kok C.Y.L. Endaya B.B. Habib A.A. Horibe T. Ng W.H. Ho I.A.W. Hui K.M. Kordula T. Lam P.Y.P. |
Keywords: | epidermal growth factor receptor epidermal growth factor receptor v III interleukin 13 interleukin 13 receptor alpha2 messenger RNA phosphatidylinositol 3 kinase protein variant STAT3 protein unclassified drug epidermal growth factor receptor epidermal growth factor receptor VIII interleukin 13 receptor alpha2 messenger RNA mitogen activated protein kinase mitogen activated protein kinase kinase kinase Raf protein Ras protein brain cancer cells and cell components enzyme enzyme activity inhibitor protein animal experiment animal model Article astrocyte cancer patient carcinogenesis cell invasion cell migration cell proliferation cell viability controlled study cytoplasm enzyme activation enzyme activity glioblastoma glioma cell line human human cell in vitro study in vivo study major clinical study MAPK signaling mouse nonhuman Pi3K/Akt signaling primary tumor protein expression protein phosphorylation signal transduction tumor xenograft U-251MG cell line animal brain tumor cancer transplantation gene knockdown genetics glioblastoma metabolism mortality mutation pathology survival rate tumor cell line tumor invasion Animals Brain Neoplasms Cell Line, Tumor Cell Proliferation Extracellular Signal-Regulated MAP Kinases Gene Knockdown Techniques Glioblastoma Humans In Vitro Techniques Interleukin-13 Receptor alpha2 Subunit MAP Kinase Kinase Kinases Mice Mutation Neoplasm Invasiveness Neoplasm Transplantation raf Kinases ras Proteins Receptor, Epidermal Growth Factor RNA, Messenger Survival Rate |
Issue Date: | 2017 | Publisher: | Nature Publishing Group | Citation: | Newman J.P., Wang G.Y., Arima K., Guan S.P., Waters M.R., Cavenee W.K., Pan E., Aliwarga E., Chong S.T., Kok C.Y.L., Endaya B.B., Habib A.A., Horibe T., Ng W.H., Ho I.A.W., Hui K.M., Kordula T., Lam P.Y.P. (2017). Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme. Nature Communications 8 (1) : 1913. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-01392-9 | Abstract: | The interleukin-13 receptor alpha2 (IL-13R?2) is a cancer-associated receptor overexpressed in human glioblastoma multiforme (GBM). This receptor is undetectable in normal brain which makes it a highly suitable target for diagnostic and therapeutic purposes. However, the pathological role of this receptor in GBM remains to be established. Here we report that IL-13R?2 alone induces invasiveness of human GBM cells without affecting their proliferation. In contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13R?2 promotes GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic domain of IL-13R?2 specifically binds to EGFRvIII, and this binding upregulates the tyrosine kinase activity of EGFRvIII and activates the RAS/RAF/MEK/ERK and STAT3 pathways. Our findings support the "To Go or To Grow" hypothesis whereby IL-13R?2 serves as a molecular switch from invasion to proliferation, and suggest that targeting both receptors with STAT3 signaling inhibitor might be a therapeutic approach for the treatment of GBM. © 2017 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174482 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-017-01392-9 |
| Appears in Collections: | Elements Staff Publications |
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