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Cited by 22Wnt/β-catenin signaling in development and cancerGene Regulatory Network AnalysisDevelopmental Biology and Gene Regulation

Computational Modeling of the Interplay between Cadherin-Mediated Cell Adhesion and Wnt Signaling Pathway

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Chen, Jiawen, Xie, Zhong-Ru, Wu, Yinghao·2014·PLoS ONE
DOI 10.1371/journal.pone.0100702PMC PMC4072676
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Abstract

Wnt signaling and cadherin-mediated adhesion have been implicated in both processes of embryonic development and the progression of carcinomas. Recent experimental studies revealed that Wnt signaling and cadherin-mediated cell adhesion have close crosstalk with each other. A comprehensive model that investigates the dynamic balance of β-catenins in Wnt signaling and cell adhesion will improve our understanding to embryonic development and carcinomas. We constructed a network model to evaluate the dynamic interplay between adhesion and Wnt signaling. The network is decomposed into three interdependent modules: the cell adhesion, the degradation circle and the transcriptional regulation. In the cell adhesion module, we consider the effect of cadherin's lateral clustering. We found adhesion negatively contributes to Wnt signaling through competition for cytoplasmic β-catenins. In the network of degradation circle, we incorporated features from various existing models. Our simulations reproduced the most recent experimental phenomena with semi-quantitative accuracy. Finally, in the transcriptional regulation module, we developed a function selection strategy to analyze the outcomes of genetic feedback loops in modulating the gene expression of Wnt targets. The specific cellular phenomena such as cadherin switch and Axin oscillation were archived and their biological insights were discussed. Our model provides the theoretical basis of how spatial organization regulates the dynamics of cellular signaling pathways. We suggest that cell adhesion affects Wnt signaling in both negative and positive ways. Cadherins can inhibit Wnt signaling not only in a way as a stoichiometric binding partner of β-catenins that sequesters them from signaling, but also in a way through their clustering to impacts the rate at which β-catenins are involved in the destruction loop. Additionally, cadherin clustering increases the phosphorylation rate of β-catenins and promotes its signaling in nucleus.

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Crossref · 10.1371/journal.pone.0100702

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  • Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].

    “Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [49]

    The Models section describes one network model made of connected modules, not multiple models presented as revisions or alternatives to one another. It also explicitly says the Wnt-stimulation module extends Lee’s earlier model, contrary to the claim that these models are neither extensions nor compositions. (LLM, conf=0.86)

    Checked by a reasoning model — may be wrong.

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  • All other models are not part of a cluster and are either completely disconnected from the other studies [31] or include E-cadherin and the cell cycle [39] or just E-cadherin [49].

    “All other models are not part of a cluster and are either completely disconnected from the other studies [31] or include E-cadherin and the cell cycle [39] or just E-cadherin [49].”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [49]

    The citation [49] is attached to the description of this model as covering “just E-cadherin.” The Discussions section (page unavailable) says the model also integrates β-catenin degradation and transcriptional regulation to study the interplay between cell adhesion and Wnt signaling. The paper therefore contradicts the “just E-cadherin” characterization. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57]).

    “Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57])”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [49]

    The Results section, under “Calibration of Wnt stimulation and β-catenin degradation module” (page unavailable), explicitly describes calibrating model parameters against experimental results. But “just calibrated” overstates the limitation: the Discussions section says the authors also used the calibrated model to investigate the interplay between cell adhesion and Wnt signaling. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Requirements could only be identified in the publications of Lee et al. (2003) [28], Wang et al. (2013) [48], Chen et al. (2014) [49], and Haack et al. (2020) [56].

    “We could only identify Requirements in the publications of Lee et al. (2003) [28], Wang et al. (2013) [48], Chen et al. (2014) [49], and Haack et al. (2020) [56].”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [49]

  • Some studies develop a story line where a simulation model has been successively refined, extended, or composed ([28, 33, 34, 36, 41, 46, 48, 49, 51, 56]).

    “Some studies develop a story line where a simulation model has been successively refined, extended, or composed ([28, 33, 34, 36, 41, 46, 48, 49, 51, 56]).”

    From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [49]

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References 74 · Cited by 22

Research works printed but not linked: 68

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Authors
Chen, J., Xie, Z.-R., & Wu, Y.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Wu, Yinghao
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-06-26
Volume
9
Issue
6
Pages
e100702
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0100702
PMC
PMC4072676
OpenAlex
W2093911514
Cited by
22
References
74
Citations by year
2026: 1 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3
FWCI
0.96
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Wnt signaling, β-catenin, transcriptional regulation, cadherin switch, β-catenin phosphorylation, network models, embryonic development, carcinogenesis
MeSH terms
Cell Adhesion, Computer Simulation, Gene Expression Regulation, Kinetics, Models, Biological, Transcription, Genetic, Cadherins, Feedback, Physiological, beta Catenin, Proteolysis, Wnt Signaling Pathway

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