Toward a quantitative understanding of the Wnt/β-catenin pathway through simulation and experiment

• Published in: Wiley interdisciplinary reviews. Mechanisms of disease 2013-07, Vol.5 (4), p.391-407
• Main Authors: Lloyd-Lewis, Bethan, Fletcher, Alexander G., Dale, Trevor C., Byrne, Helen M.
• Format: Article
• Language: English
• Subjects: Aberration; beta Catenin - metabolism; Biological effects; Cancer; Carcinogenesis; Carcinogens; Catenin; Cell Communication; Cell culture; Cell Cycle; Cell surface; Cell survival; Complexity; Computer applications; Computer simulation; Developmental biology; Differential equations; Homeostasis; Humans; Mathematical analysis; Mathematical models; Models, Theoretical; Mutation; Ordinary differential equations; Receptors; Signal transduction; Signaling; Transcription; Wnt protein; Wnt Proteins - metabolism; Wnt Signaling Pathway
• ISSN: 1939-5094; 1939-005X; 2692-9368
• DOI: 10.1002/wsbm.1221

Wnt signaling regulates cell survival, proliferation, and differentiation throughout development and is aberrantly regulated in cancer. The pathway is activated when Wnt ligands bind to specific receptors on the cell surface, resulting in the stabilization and nuclear accumulation of the transcriptional co‐activator β‐catenin. Mathematical and computational models have been used to study the spatial and temporal regulation of the Wnt/β‐catenin pathway and to investigate the functional impact of mutations in key components. Such models range in complexity, from time‐dependent, ordinary differential equations that describe the biochemical interactions between key pathway components within a single cell, to complex, multiscale models that incorporate the role of the Wnt/β‐catenin pathway target genes in tissue homeostasis and carcinogenesis. This review aims to summarize recent progress in mathematical modeling of the Wnt pathway and to highlight new biological results that could form the basis for future theoretical investigations designed to increase the utility of theoretical models of Wnt signaling in the biomedical arena. WIREs Syst Biol Med 2013, 5:391–407. doi: 10.1002/wsbm.1221 This article is categorized under: Biological Mechanisms > Cell Signaling Developmental Biology > Lineages Models of Systems Properties and Processes > Mechanistic Models