Format

Send to

Choose Destination
BMC Syst Biol. 2017 Sep 21;11(Suppl 4):84. doi: 10.1186/s12918-017-0457-6.

Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

Author information

1
Department of Mathematics, Shanghai University, No.99, Shangda Road, Shanghai, 200444, China.
2
Department of Mathematics, Shanghai University, No.99, Shangda Road, Shanghai, 200444, China. rqwang@shu.edu.cn.

Abstract

BACKGROUND:

The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition.

RESULTS:

This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas.

CONCLUSIONS:

This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

KEYWORDS:

Cis-inhibition; Fringe; Gliomas; Notch; Trans-activation

PMID:
28950865
PMCID:
PMC5615248
DOI:
10.1186/s12918-017-0457-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center