Title |
EGFR Phosphorylates Tumor-Derived EGFRvIII Driving STAT3/5 and Progression in Glioblastoma
|
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Published in |
Cancer Cell, October 2013
|
DOI | 10.1016/j.ccr.2013.09.004 |
Pubmed ID | |
Authors |
Qi-Wen Fan, Christine K. Cheng, W. Clay Gustafson, Elizabeth Charron, Petra Zipper, Robyn A. Wong, Justin Chen, Jasmine Lau, Christiane Knobbe-Thomsen, Michael Weller, Natalia Jura, Guido Reifenberger, Kevan M. Shokat, William A. Weiss |
Abstract |
EGFRvIII, a frequently occurring mutation in primary glioblastoma, results in a protein product that cannot bind ligand, but signals constitutively. Deducing how EGFRvIII causes transformation has been difficult because of autocrine and paracrine loops triggered by EGFRvIII alone or in heterodimers with wild-type EGFR. Here, we document coexpression of EGFR and EGFRvIII in primary human glioblastoma that drives transformation and tumorigenesis in a cell-intrinsic manner. We demonstrate enhancement of downstream STAT signaling triggered by EGFR-catalyzed phosphorylation of EGFRvIII, implicating EGFRvIII as a substrate for EGFR. Subsequent phosphorylation of STAT3 requires nuclear entry of EGFRvIII and formation of an EGFRvIII-STAT3 nuclear complex. Our findings clarify specific oncogenic signaling relationships between EGFR and EGFRvIII in glioblastoma. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 25% |
India | 1 | 13% |
Hungary | 1 | 13% |
Unknown | 4 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 7 | 88% |
Scientists | 1 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 1% |
United States | 2 | <1% |
Hong Kong | 1 | <1% |
Spain | 1 | <1% |
Canada | 1 | <1% |
Unknown | 229 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 57 | 24% |
Researcher | 53 | 22% |
Student > Master | 20 | 8% |
Student > Bachelor | 19 | 8% |
Other | 17 | 7% |
Other | 26 | 11% |
Unknown | 45 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 57 | 24% |
Biochemistry, Genetics and Molecular Biology | 49 | 21% |
Medicine and Dentistry | 40 | 17% |
Neuroscience | 9 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 3% |
Other | 26 | 11% |
Unknown | 48 | 20% |