RETRACTED: Funneled Landscape Leads to Robustness of Cellular Networks: MAPK Signal Transduction

Wang, Jin; Huang, Bo; Xia, Xuefeng; Sun, Zhirong

doi:10.1529/biophysj.106.086777

Cited by 35 publications

(41 citation statements)

References 12 publications

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“…Even after mutations in its genome, it may still stay in the lysogenic state for many generations [38,50]. Thus, the existence of functional landscape with multiple stable states explains the robustness widely observed in biological systems [16,21,[51][52][53][54][55]. The existence of such multiple stable states may also corroborate well with the observations that cancer takes multiple steps [56]: If regarding moving from one stable state to another as one step.…”

Section: Discussionsupporting

confidence: 61%

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Ao¹,

Galas²,

Hood³

et al. 2008

Medical Hypotheses

145

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SummaryAn endogenous molecular-cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or abnormal robust states can be decided by this network in a manner similar to the neural network. In this context cancer is hypothesized as one of its robust intrinsic states.This hypothesis implies that a nonlinear stochastic mathematical cancer model is constructible based on available experimental data and its quantitative prediction is directly testable. Within such model the genesis and progression of cancer may be viewed as stochastic transitions between different attractors. Thus it further suggests that progressions are not arbitrary. Other important issues on cancer, such as genetic vs epigenetics, double-edge effect, dormancy, are discussed in the light of present hypothesis. A different set of strategies for cancer prevention, cure, and care, is therefore suggested.

show abstract

Section: Discussionsupporting

confidence: 61%

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Ao¹,

Galas²,

Hood³

et al. 2008

Medical Hypotheses

145

View full text Add to dashboard Cite

show abstract

“…The potential energy function U(x) (14,(18)(19)(20)(21)(22)(23)33) can be related to steady-state probability:…”

Section: Resultsmentioning

confidence: 99%

“…From the engineering perspective, efforts have been made to understand the network from control perspectives with robust yet fragile natures (10). There have been a number of studies attempting to determine why networks are robust in their biological function among perturbations (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

“…Thus, it is necessary to move from a deterministic model to a statistical model. The study of the influence under external noise from the cellular environments for the MAPK system was carried out in an earlier article (19). Here, we will focus on the intrinsic noise from number fluctuation.…”

mentioning

confidence: 99%

“…To describe the system under noisy conditions, we will define a potential energy function that is derived from the steady-state probability of the network. After this landscape is determined, the probability of each state is known and we can begin to analyze global features (19,22,23). This is reminiscent of equilibrium systems, where one can analyze the phase diagram and other global features.…”

mentioning

confidence: 99%

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Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction

Lapidus

Han

Wang

2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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We develop a probabilistic method for analyzing global features of a cellular network under intrinsic statistical fluctuations, which is important when there are finite numbers of molecules. By making a self-consistent mean field approximation of splitting the variables in order to reduce the large number of degrees of freedom, which is reasonable for a not very strongly interacting network, we discovered that the underlying energy landscape of the mitogen-activated protein kinases (MAPKs) signal transduction network (with experimentally measured or inferred parameters such as chemical reaction rate coefficients in the network) is funneled toward a global minimum characterized by the nonequilibrium steady-state fixed point of the system at the end of the signal transduction process. For this system, we also show that the energy landscape is robust against intrinsic fluctuations and random perturbation to the inherent chemical reaction rates. The ratio of the slope versus the roughness of the energy landscape becomes a quantitative measure of robustness and stability of the network. Furthermore, we quantify the dissipation cost of this nonequilibrium system through entropy production, caused by the nonequilibrium flux in the system. We found that a lower dissipation cost corresponds to a more robust network. This least dissipation property might provide a design principle for robust and functional networks. Finally, we find the possibility of bistable and oscillatory-like solutions, which are important for cell fate decisions, upon perturbations. The method described here can be used in a variety of biological networks.funnel ͉ stability ͉ potential landscape ͉ function

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Biocomputing: Explore Its Realization and Intelligent Logic Detection

Zhou

Dong

2012

Biomolecular Information Processing

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RETRACTED: Funneled Landscape Leads to Robustness of Cellular Networks: MAPK Signal Transduction

Cited by 35 publications

References 12 publications

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction

Biocomputing: Explore Its Realization and Intelligent Logic Detection

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