A cell-autonomous positive-signaling circuit associated with the PDGF-NO-ID4-regulatory axis in glioblastoma cells
- Authors
- Eun, Kiyoung; Jeon, Hye-Min; Kim, Sung-Ok; Choi, Sang-Hun; Lee, Seon Yong; Jin, Xiong; Kim, Sung-Chan; Kim, Hyunggee
- Issue Date
- 29-4월-2017
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Cell-signaling circuit; Glioblastoma cells; Inhibitor of differentiation 4; Nitric oxide; Platelet-derived growth factor
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.486, no.2, pp.564 - 570
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 486
- Number
- 2
- Start Page
- 564
- End Page
- 570
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/83713
- DOI
- 10.1016/j.bbrc.2017.03.089
- ISSN
- 0006-291X
- 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 PDGFR alpha, 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. (C) 2017 Elsevier Inc. All rights reserved.
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