Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway

Jiawen Chen, Zhong Ru Xie, Yinghao Wu

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere100702
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 26 2014

Fingerprint

Wnt Signaling Pathway
cadherins
Cell adhesion
Catenins
Cadherins
cell adhesion
Cell Adhesion
Cluster Analysis
adhesion
carcinoma
Embryonic Development
embryogenesis
Adhesion
Carcinoma
cell communication
degradation
dynamic models
Cell signaling
oscillation
Degradation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway. / Chen, Jiawen; Xie, Zhong Ru; Wu, Yinghao.

In: PLoS One, Vol. 9, No. 6, e100702, 26.06.2014.

Research output: Contribution to journalArticle

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