A novel EGFR isoform confers increased invasiveness to cancer cells.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zhou, M; Wang, H; Zhou, K; Luo, X; Pan, X; Shi, B; Jiang, H; Zhang, J; Li, K; Wang, H-M; Gao, H; Lu, S; Yao, M; Mao, Y; Wang, H-Y; Yang, S; Gu, J; Li, C; Li, Z

Published Date

  • December 1, 2013

Published In

Volume / Issue

  • 73 / 23

Start / End Page

  • 7056 - 7067

PubMed ID

  • 24240702

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-13-0194


  • eng

Conference Location

  • United States