A cell-autonomous positive-signaling circuit associated with the PDGF-NO-ID4-regulatory axis in glioblastoma cells

Kiyoung Eun, Hye Min Jeon, Sung Ok Kim, Sang Hun Choi, Seon Yong Lee, Xiong Jin, Sung Chan Kim, Hyunggee Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit. ID4 expression significantly increased PDGF subunit B expression in both in vitro cultures and in vivo tumor xenografts and regulated NO synthase 2 (NOS2) expression and NO production by activating PDGF signaling, as well as that of its receptor (PDGFR). Additionally, ectopic expression of PDGFRα, NOS2, or ID4 activated the PDGF-NO-ID4-signaling circuit and enhanced the self-renewal of GBM cell lines. These results suggested that the positive regulatory circuit associated with PDGF-NO-ID4 signaling plays a pivotal role in regulating the self-renewal and tumor-initiating capacity of GSCs and might provide a promising therapeutic target for GBM.

Original languageEnglish
Pages (from-to)564-570
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume486
Issue number2
DOIs
Publication statusPublished - 2017 Apr 29

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Keywords

  • Cell-signaling circuit
  • Glioblastoma cells
  • Inhibitor of differentiation 4
  • Nitric oxide
  • Platelet-derived growth factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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