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

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...

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Autores principales:	Jiawen Chen, Zhong-Ru Xie, Yinghao Wu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dad2cfcc6ded413e97f935477dd1ea76
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spelling	oai:doaj.org-article:dad2cfcc6ded413e97f935477dd1ea762021-11-11T08:21:30ZComputational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.1932-620310.1371/journal.pone.0100702https://doaj.org/article/dad2cfcc6ded413e97f935477dd1ea762014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24967587/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Wnt 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.Jiawen ChenZhong-Ru XieYinghao WuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e100702 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiawen Chen Zhong-Ru Xie Yinghao Wu Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
description	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.
format	article
author	Jiawen Chen Zhong-Ru Xie Yinghao Wu
author_facet	Jiawen Chen Zhong-Ru Xie Yinghao Wu
author_sort	Jiawen Chen
title	Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
title_short	Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
title_full	Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
title_fullStr	Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
title_full_unstemmed	Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.
title_sort	computational modeling of the interplay between cadherin-mediated cell adhesion and wnt signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/dad2cfcc6ded413e97f935477dd1ea76
work_keys_str_mv	AT jiawenchen computationalmodelingoftheinterplaybetweencadherinmediatedcelladhesionandwntsignalingpathway AT zhongruxie computationalmodelingoftheinterplaybetweencadherinmediatedcelladhesionandwntsignalingpathway AT yinghaowu computationalmodelingoftheinterplaybetweencadherinmediatedcelladhesionandwntsignalingpathway
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Computational modeling of the interplay between cadherin-mediated cell adhesion and Wnt signaling pathway.

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