Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling

PloS One
Annika JacobsenK Anton Feenstra

Abstract

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulat...Continue Reading

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Related Concepts

CTNNB1 protein, human
In Silico
Beta catenin
HEK293 Cells
Wnt beta-Catenin Signaling Pathway
Malignant Neoplasm of Breast
Malignant Neoplasms
Plasma Membrane
Cytoplasm
Genes

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