ERK‑mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells

  • Authors:
    • Ratna Dini Haryuni
    • Tomohiro Tanaka
    • Yue Zhou
    • Satoru Yokoyama
    • Hiroaki Sakurai
  • View Affiliations

  • Published online on: June 19, 2020     https://doi.org/10.3892/ol.2020.11760
  • Pages: 2477-2482
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Epidermal growth factor receptor variant III (EGFRvIII) is the most common active EGFR mutant in glioblastoma multiforme (GBM). The expression of this mutant often correlates with a poor patient prognosis due to its ability to extend downstream signaling. The EGFR pathway is controlled by a negative feedback mechanism that restricts the extent and length of downstream signaling. To date, the role of negative feedback in the oncogenic EGFRvIII mutant remains undetermined. The present study indicated that activation of the MEK‑ERK pathway led to the phosphorylation of Thr‑402, a conserved negative feedback residue in the juxtamembrane domain corresponding to Thr‑669 of wild‑type EGFR (EGFRwt), which resulted in a rapid reduction in the tyrosine phosphorylation of EGFRvIII in U87MG human glioblastoma and 293 cells. Moreover, despite the incapability of EGFRvIII to bind ligands, EGF was indicated to downregulate the tyrosine phosphorylation of EGFRvIII by activating the EGFRwt‑ERK pathway. These results demonstrated a conserved negative feedback mechanism in the activation of EGFRvIII, which presents a new aspect in functional interactions between EGFRvIII and EGFRwt in glioblastoma cells.

Related Articles

Journal Cover

September-2020
Volume 20 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Haryuni RD, Tanaka T, Zhou Y, Yokoyama S and Sakurai H: ERK‑mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells. Oncol Lett 20: 2477-2482, 2020
APA
Haryuni, R.D., Tanaka, T., Zhou, Y., Yokoyama, S., & Sakurai, H. (2020). ERK‑mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells. Oncology Letters, 20, 2477-2482. https://doi.org/10.3892/ol.2020.11760
MLA
Haryuni, R. D., Tanaka, T., Zhou, Y., Yokoyama, S., Sakurai, H."ERK‑mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells". Oncology Letters 20.3 (2020): 2477-2482.
Chicago
Haryuni, R. D., Tanaka, T., Zhou, Y., Yokoyama, S., Sakurai, H."ERK‑mediated negative feedback regulation of oncogenic EGFRvIII in glioblastoma cells". Oncology Letters 20, no. 3 (2020): 2477-2482. https://doi.org/10.3892/ol.2020.11760