Header

UZH-Logo

Maintenance Infos

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


Fan, Q W; Cheng, C K; Gustafson, W C; Charron, E; Zipper, P; Wong, R A; Chen, J; Lau, J; Knobbe-Thomsen, C; Weller, M; Jura, N; Reifenberger, G; Shokat, K M; Weiss, W A (2013). EGFR Phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma. Cancer Cell, 24(4):438-449.

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.

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.

Statistics

Citations

75 citations in Web of Science®
76 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

296 downloads since deposited on 26 Nov 2013
57 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:26 Nov 2013 14:14
Last Modified:06 Aug 2017 09:50
Publisher:Cell Press (Elsevier)
ISSN:1535-6108
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ccr.2013.09.004
PubMed ID:24135280

Download

Download PDF  'EGFR Phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 2MB
View at publisher