Please use this identifier to cite or link to this item: 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
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