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Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme

The interleukin-13 receptor alpha2 (IL-13Rα2) 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 re...

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Autores principales: Newman, Jennifer P., Wang, Grace Y., Arima, Kazuhiko, Guan, Shou P., Waters, Michael R., Cavenee, Webster K., Pan, Edward, Aliwarga, Edita, Chong, Siao T., Kok, Catherine Y. L., Endaya, Berwini B., Habib, Amyn A., Horibe, Tomohisa, Ng, Wai H., Ho, Ivy A. W., Hui, Kam M., Kordula, Tomasz, Lam, Paula Y. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715073/
https://www.ncbi.nlm.nih.gov/pubmed/29203859
http://dx.doi.org/10.1038/s41467-017-01392-9
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author Newman, Jennifer P.
Wang, Grace Y.
Arima, Kazuhiko
Guan, Shou P.
Waters, Michael R.
Cavenee, Webster K.
Pan, Edward
Aliwarga, Edita
Chong, Siao T.
Kok, Catherine Y. L.
Endaya, Berwini B.
Habib, Amyn A.
Horibe, Tomohisa
Ng, Wai H.
Ho, Ivy A. W.
Hui, Kam M.
Kordula, Tomasz
Lam, Paula Y. P.
author_facet Newman, Jennifer P.
Wang, Grace Y.
Arima, Kazuhiko
Guan, Shou P.
Waters, Michael R.
Cavenee, Webster K.
Pan, Edward
Aliwarga, Edita
Chong, Siao T.
Kok, Catherine Y. L.
Endaya, Berwini B.
Habib, Amyn A.
Horibe, Tomohisa
Ng, Wai H.
Ho, Ivy A. W.
Hui, Kam M.
Kordula, Tomasz
Lam, Paula Y. P.
author_sort Newman, Jennifer P.
collection PubMed
description The interleukin-13 receptor alpha2 (IL-13Rα2) 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-13Rα2 alone induces invasiveness of human GBM cells without affecting their proliferation. In contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13Rα2 promotes GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic domain of IL-13Rα2 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-13Rα2 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.
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spelling pubmed-57150732017-12-06 Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme Newman, Jennifer P. Wang, Grace Y. Arima, Kazuhiko Guan, Shou P. Waters, Michael R. Cavenee, Webster K. Pan, Edward Aliwarga, Edita Chong, Siao T. Kok, Catherine Y. L. Endaya, Berwini B. Habib, Amyn A. Horibe, Tomohisa Ng, Wai H. Ho, Ivy A. W. Hui, Kam M. Kordula, Tomasz Lam, Paula Y. P. Nat Commun Article The interleukin-13 receptor alpha2 (IL-13Rα2) 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-13Rα2 alone induces invasiveness of human GBM cells without affecting their proliferation. In contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13Rα2 promotes GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic domain of IL-13Rα2 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-13Rα2 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. Nature Publishing Group UK 2017-12-04 /pmc/articles/PMC5715073/ /pubmed/29203859 http://dx.doi.org/10.1038/s41467-017-01392-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Newman, Jennifer P.
Wang, Grace Y.
Arima, Kazuhiko
Guan, Shou P.
Waters, Michael R.
Cavenee, Webster K.
Pan, Edward
Aliwarga, Edita
Chong, Siao T.
Kok, Catherine Y. L.
Endaya, Berwini B.
Habib, Amyn A.
Horibe, Tomohisa
Ng, Wai H.
Ho, Ivy A. W.
Hui, Kam M.
Kordula, Tomasz
Lam, Paula Y. P.
Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title_full Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title_fullStr Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title_full_unstemmed Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title_short Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme
title_sort interleukin-13 receptor alpha 2 cooperates with egfrviii signaling to promote glioblastoma multiforme
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715073/
https://www.ncbi.nlm.nih.gov/pubmed/29203859
http://dx.doi.org/10.1038/s41467-017-01392-9
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