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Cited by 281

The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.

Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition

Open access
Tian, Xiao-Jun, Zhang, Hang, Xing, Jianhua·2013·Biophysical Journal

Abstract

Epithelial to mesenchymal transition (EMT) plays an important role in embryonic development, tissue regeneration, and cancer metastasis. Whereas several feedback loops have been shown to regulate EMT, it remains elusive how they coordinately modulate EMT response to TGF-β treatment. We construct a mathematical model for the core regulatory network controlling TGF-β-induced EMT. Through deterministic analyses and stochastic simulations, we show that EMT is a sequential two-step program in which an epithelial cell first is converted to partial EMT then to the mesenchymal state, depending on the strength and duration of TGF-β stimulation. Mechanistically the system is governed by coupled reversible and irreversible bistable switches. The SNAIL1/miR-34 double-negative feedback loop is responsible for the reversible switch and regulates the initiation of EMT, whereas the ZEB/miR-200 feedback loop is accountable for the irreversible switch and controls the establishment of the mesenchymal state. Furthermore, an autocrine TGF-β/miR-200 feedback loop makes the second switch irreversible, modulating the maintenance of EMT. Such coupled bistable switches are robust to parameter variation and molecular noise. We provide a mechanistic explanation on multiple experimental observations. The model makes several explicit predictions on hysteretic dynamic behaviors, system response to pulsed stimulation, and various perturbations, which can be straightforwardly tested.

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Metadata

Authors
Tian, X.-J., Zhang, H., & Xing, J.
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2013-08
Volume
105
Issue
4
Pages
1079-1089
ISSN
0006-3495 (ISSN-L)
OpenAlex
W1980561748
Cited by
281
References
77
FWCI
4.84
Type
journal article
Language
en
Open access
bronze
Licence

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CoChat. (2026). Citation check: Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition. https://app.cochat.ai/papers/10.1016/j.bpj.2013.07.011
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Tian, X.-J., Zhang, H., & Xing, J. (2013). Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition. Biophysical Journal. https://doi.org/10.1016/j.bpj.2013.07.011

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.