Open AccessA structural model of the VEGF signalling pathway: Emergence of robustness and redundancy properties
Author(s) -
Floriane Lignet,
Vincent Cálvez,
Emmanuel Grenier,
Benjamin Ribba
Publication year - 2013
Publication title -
mathematical biosciences and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 45
eISSN - 1551-0018
pISSN - 1547-1063
DOI - 10.3934/mbe.2013.10.167
Subject(s) - angiogenesis , signalling , robustness (evolution) , vegf receptors , vascular endothelial growth factor , apoptosis , redundancy (engineering) , biology , microbiology and biotechnology , metastasis , vascular endothelial growth factor a , signal transduction , cancer research , computer science , computational biology , genetics , cancer , gene , operating system
The vascular endothelial growth factor (VEGF) is known as one of the main promoter of angiogenesis - the process of blood vessel formation. Angiogenesis has been recognized as a key stage for cancer development and metastasis. In this paper, we propose a structural model of the main molecular pathways involved in the endothelial cells response to VEGF stimuli. The model, built on qualitative information from knowledge databases, is composed of 38 ordinary differential equations with 78 parameters and focuses on the signalling driving endothelial cell proliferation, migration and resistance to apoptosis. Following a VEGF stimulus, the model predicts an increase of proliferation and migration capability, and a decrease in the apoptosis activity. Model simulations and sensitivity analysis highlight the emergence of robustness and redundancy properties of the pathway. If further calibrated and validated, this model could serve as tool to analyse and formulate new hypothesis on th e VEGF signalling cascade and its role in cancer development and treatment.