Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16773
Title: Control of glioblastoma tumorigenesis by feed-forward cytokine signaling
Austin Authors: Jahani-Asl, Arezu;Yin, Hang;Soleimani, Vahab D;Haque, Takrima;Luchman, H Artee;Chang, Natasha C;Sincennes, Marie-Claude;Puram, Sidharth V;Scott, Andrew M ;Lorimer, Ian A J;Perkins, Theodore J;Ligon, Keith L;Weiss, Samuel;Rudnicki, Michael A;Bonni, Azad
Affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA
Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri, USA
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Department of Oncology, McGill University, Montreal, Quebec, Canada
Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
Department of Biochemistry, University of Georgia, Athens, Georgia, USA
Molecular Biology Centre for Molecular Medicine, University of Georgia, Athens, Georgia, USA
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
Department of Cell Biology &Anatomy, University of Calgary, Calgary, Alberta, Canada
Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, Australia
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
Issue Date: Jun-2016
metadata.dc.date: 2016-04-25
Publication information: Nature Neuroscience 2016; 19(6): 798-806
Abstract: EGFRvIII-STAT3 signaling is important in glioblastoma pathogenesis. Here, we identified the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). We found that OSMR functioned as an essential co-receptor for EGFRvIII. OSMR formed a physical complex with EGFRvIII, and depletion of OSMR impaired EGFRvIII-STAT3 signaling. Conversely, pharmacological inhibition of EGFRvIII phosphorylation inhibited the EGFRvIII-OSMR interaction and activation of STAT3. EGFRvIII-OSMR signaling in tumors operated constitutively, whereas EGFR-OSMR signaling in nontumor cells was synergistically activated by the ligands EGF and OSM. Finally, knockdown of OSMR strongly suppressed cell proliferation and tumor growth of mouse glioblastoma cells and human BTSC xenografts in mice, and prolonged the lifespan of these mice. Our findings identify OSMR as a critical regulator of glioblastoma tumor growth that orchestrates a feed-forward signaling mechanism with EGFRvIII and STAT3 to drive tumorigenesis.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16773
DOI: 10.1038/nn.4295
ORCID: 0000-0002-6656-295X
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/27110918
Type: Journal Article
Subjects: Brain Neoplasms
Cell Transformation, Neoplastic
Cytokines
Glioblastoma
Signal Transduction
Appears in Collections:Journal articles

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