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Cancer Cell. 2013 Oct 14;24(4):438-49. doi: 10.1016/j.ccr.2013.09.004.

EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma.

Author information

1
Department of Neurology, University of California, San Francisco, 1450 Third Street, MC0520, San Francisco, CA 94158-9001, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, MC0520, San Francisco, CA 94158-9001, USA. Electronic address: qiwen.fan@ucsf.edu.

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.

PMID:
24135280
PMCID:
PMC3819146
DOI:
10.1016/j.ccr.2013.09.004
[Indexed for MEDLINE]
Free PMC Article

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