A novel EGFR isoform confers increased invasiveness to cancer cells.
As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform termed EGFRvA, which substitutes a Ser/Thr-rich peptide for part of the carboxyl-terminal regulatory domain of the receptor. Intriguingly, EGFRvA expression relates more closely to histopathologic grade and poor prognosis in patients with glioma. Ectopic expression of EGFRvA in cancer cells conferred a higher invasive capacity than EGFR in vitro and in vivo. Mechanistically, EGFRvA stimulated expression of STAT3, which upregulated heparin-binding EGF (HB-EGF). Reciprocally, HB-EGF stimulated phosphorylation of EGFRvA at Y845 along with STAT3, generating a positive feedback loop that may reinforce invasive function. The significance of EGFRvA expression was reinforced by findings that it is attenuated by miR-542-5p, a microRNA that is a known tumor suppressor. Taken together, our findings define this newfound EGFR isoform as a key theranostic molecule.
Duke Scholars
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- Tumor Cells, Cultured
- Survival Analysis
- Signal Transduction
- STAT3 Transcription Factor
- Protein Isoforms
- Prognosis
- Oncology & Carcinogenesis
- Neoplasms
- Neoplasm Invasiveness
- NIH 3T3 Cells
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Survival Analysis
- Signal Transduction
- STAT3 Transcription Factor
- Protein Isoforms
- Prognosis
- Oncology & Carcinogenesis
- Neoplasms
- Neoplasm Invasiveness
- NIH 3T3 Cells