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Cancer invasion and metastasis depend on angiogenesis. The cellular processes (growth, migration, and apoptosis) that occur during angiogenesis are tightly regulated by signaling molecules. Thus, understanding how cells synthesize multiple biochemical signals initiated by key external stimuli can lead to the development of novel therapeutic strategies to combat cancer. In the face of large amounts of disjoint experimental data generated from multitudes of laboratories using various assays, theoretical signal transduction models provide a framework to distill this vast amount of data. Such models offer an opportunity to formulate and test new hypotheses, and can be used to make experimentally verifiable predictions. This study is the first to propose a network model that highlights the cross-talk between the key receptors involved in angiogenesis, namely growth factor, integrin, and cadherin receptors. From available experimental data, we construct a stochastic Boolean network model of receptor cross-talk, and systematically analyze the dynamical stability of the network under continuous-time Boolean dynamics with a noisy production function. We find that the signal transduction network exhibits a robust and fast response to external signals, independent of the internal cell state. We derive an input-output table that maps external stimuli to cell phenotypes, which is extraordinarily stable against molecular noise with one important exception: an oscillatory feedback loop between the key signaling molecules RhoA and Rac1 is unstable under arbitrarily low noise, leading to erratic, dysfunctional cell motion. Finally, we show that the network exhibits an apoptotic response rate that increases with noise, suggesting that the probability of programmed cell death depends on cell health.
Genetic regulation is a key component in development, but a clear understanding of the structure and dynamics of genetic networks is not yet at hand. In this paper we investigate these properties within an artificial genome model originally introduce
Based on a non-equilibrium mechanism for spatial pattern formation we study how position information can be controlled by locally coupled discrete dynamical networks, similar to gene regulation networks of cells in a developing multicellular organism
Complex systems are often modeled as Boolean networks in attempts to capture their logical structure and reveal its dynamical consequences. Approximating the dynamics of continuous variables by discrete values and Boolean logic gates may, however, in
During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and glo
Genetic regulation is a key component in development, but a clear understanding of the structure and dynamics of genetic networks is not yet at hand. In this work we investigate these properties within an artificial genome model originally introduced