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Erschienen in: Tumor Biology 4/2015

01.04.2015 | Research Article

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

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

Erschienen in: Tumor Biology | Ausgabe 4/2015

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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.
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Metadaten
Titel
Epidermal growth factor receptor variant III renders glioma cancer cells less differentiated by JAGGED1
verfasst von
Eun-Jung Kim
Sung-Ok Kim
Xiong Jin
Seok Won Ham
Jaebong Kim
Jae-Bong Park
Jae-Yong Lee
Sung-Chan Kim
Hyunggee Kim
Publikationsdatum
01.04.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2922-9

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