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

Eun Jung Kim, Sung Ok Kim, Xiong Jin, Seok Won Ham, Jaebong Kim, Jae Bong Park, Jae Yong Lee, Sung Chan Kim, Hyunggee Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2921-2928
Number of pages8
JournalTumor Biology
Volume36
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

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Keywords

  • EGFRvIII
  • Glioblastoma
  • Glioma stem cells
  • JAGGED1
  • MAPK signaling
  • Radioresistance

ASJC Scopus subject areas

  • Cancer Research

Cite this

Kim, E. J., Kim, S. O., Jin, X., Ham, S. W., Kim, J., Park, J. B., Lee, J. Y., Kim, S. C., & Kim, H. (2015). Epidermal growth factor receptor variant III renders glioma cancer cells less differentiated by JAGGED1. Tumor Biology, 36(4), 2921-2928. https://doi.org/10.1007/s13277-014-2922-9