title: A structural model of the VEGF signalling pathway: emergence of robustness and redundancy properties.
abstract: 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.
authors: INRIA, Project-team NUMED, Ecole Normale Superieure de Lyon, 46 allee d'Italie, 69007 Lyon Cedex 07, France.
authors: Floriane
authors: F
authors: Lignet
authors: Vincent
authors: V
authors: Calvez
authors: Emmanuel
authors: E
authors: Grenier
authors: Benjamin
authors: B
authors: Ribba
mesh_terms: D002138:Calibration; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003198:Computer Simulation; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D020935:MAP Kinase Signaling System; D008495:Medical Oncology / Q000379:methods; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015203:Reproducibility of Results; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A