Affordable Access

deepdyve-link
Publisher Website

Epidermal growth factor receptor variant III renders glioma cancer cells less differentiated by JAGGED1.

Authors
  • Kim, Eun-Jung
  • Kim, Sung-Ok
  • Jin, Xiong
  • Ham, Seok Won
  • Kim, Jaebong
  • Park, Jae-Bong
  • Lee, Jae-Yong
  • Kim, Sung-Chan
  • Kim, Hyunggee
Type
Published Article
Journal
Tumor Biology
Publisher
SAGE Publications
Publication Date
Apr 01, 2015
Volume
36
Issue
4
Pages
2921–2928
Identifiers
DOI: 10.1007/s13277-014-2922-9
PMID: 25514871
Source
Medline
License
Unknown

Abstract

Glioblastoma is a highly aggressive primary brain tumor in which the majority of cancer cells are undifferentiated. One of the most common oncogenic drivers for this malignancy is the epidermal growth factor receptor variant III (EGFRvIII), which lacks a portion of the extracellular ligand-binding domain due to deletion of exons 2-7 of the EGFR gene. EGFRvIII plays a critical role in tumor progression, promoting acquisition of stem cell-like features including an undifferentiated state and therapy resistance. However, the molecular mechanisms by which EGFRvIII contributes to cancer cell aggressiveness remain poorly understood. Here, we show that EGFR expression correlates with JAGGED1 expression in glioblastoma patients. Overexpression of EGFRvIII in glioma cell lines augmented JAGGED1 expression at the transcriptional level through the mitogen-activated protein kinase signaling pathway. Consequently, EGFRvIII overexpression drove partial dedifferentiation of glioma cells, as determined by tumorsphere-forming ability and expression of stem cell markers, through JAGGED1 induction. EGFRvIII-mediated radioresistance, but not chemoresistance, was also modulated by JAGGED1. Taken together, our results provide new insight into the mechanism underlying EGFRvIII-driven glioblastoma aggressiveness.

Report this publication

Statistics

Seen <100 times