Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression

Xun Jin, Xiong Jin, Young Woo Sohn, Jinlong Yin, Sung Hak Kim, Kaushal Joshi, Do Hyun Nam, Ichiro Nakano, Hyunggee Kim

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression.

Original languageEnglish
Pages (from-to)235-242
Number of pages8
JournalCancer Letters
Volume328
Issue number2
DOIs
Publication statusPublished - 2013 Jan 28

Keywords

  • EGFR
  • Glioblastoma
  • Glioma stem cells
  • ID3
  • Invasion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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