@article{612081b8133b49de9b86e18c4047d62b,
title = "Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme",
abstract = "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.",
author = "Newman, {Jennifer P.} and Wang, {Grace Y.} and Kazuhiko Arima and Guan, {Shou P.} and Waters, {Michael R.} and Cavenee, {Webster K.} and Edward Pan and Edita Aliwarga and Chong, {Siao T.} and Kok, {Catherine Y.L.} and Endaya, {Berwini B.} and Habib, {Amyn A.} and Tomohisa Horibe and Ng, {Wai H.} and Ho, {Ivy A.W.} and Hui, {Kam M.} and Tomasz Kordula and Lam, {Paula Y.P.}",
note = "Funding Information: We would like to express our gratitude to Martine F. Roussel (St. Jude Childrens{\textquoteright} Research Hospital) for her constructive comments and proofreading, Malcolm Paterson (ex-director of Singhealth Office of Research), YiBin Kang (Princeton University, USA), Xandra O. Breakefield (Harvard Medical School, USA), Miguel Sena-Esteves (Massa-chusettes Medical School, USA), Kawakami K (Kyoto University, Japan), G.Eric Blair (University of Leeds, UK) for their suggestions and support. Special thanks to Frank Funari (UCSD, USA), Gan SU and Sia KC (NUS, Singapore), Linn YC (SGH, Singapore) and Wu XF (HSA, Singapore) biostatiscians and colleagues at NCCS especially Huynh H, Caroline Lee, and researchers from Hummingbird Bioscience Pte Ltd for useful discussions. The authors wish to acknowledge Mark Schroeder and Jann Sarkaria (Mayo Clinic, Rochester, Minnesota) for providing the GBM samples. This project was funded by grants from A*Star (07/1/31/19/547), Singhealth Grant Foundation, and institutional center grant from the National Medical Research Council of Singapore awarded to P.Y.P. L. This work was also supported by grant from the National Institute of Health R01AI093718 awarded to T.K. and in part, by a grant awarded to Amyn A Habib from the Department of Veteran{\textquoteright}s Affairs (I01BX002559).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41467-017-01392-9",
language = "English (US)",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}