ArticleBiophysical journal2013
Coupled reversible and irreversible bistable switches underlying TGFβ-induced epithelial to mesenchymal transition.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
164 citing papers in PubMed, 312 citations in OpenAlex.
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- Dissecting reversible and irreversible single cell state transitions from gene regulatory networks.Molecular systems biology · 2026Article
- Network hypermotifs in biological systems: structure, dynamics, and functional implications.NPJ systems biology and applications · 2026Review
- The Role of Fibroblast-Epithelial Cross-Talk on the Distribution of Distinct Fibroblast Phenotypes in the Intestinal Crypt.Bulletin of mathematical biology · 2026Article
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Wuweizisu B for cancer treatment from multitarget mechanisms to precision delivery strategies (Review).International journal of molecular medicine · 2025Review
- Mapping the Progression of Therapy-Induced Senescence to Therapy Tolerance: An Evolutionarily Conserved Mechanism for Optimizing Cancer Treatment with Senotherapeutics.ACS pharmacology & translational science · 2025Article
- SOX10, MITF, and microRNAs: Decoding their interplay in regulating melanoma plasticity.International journal of cancer · 2025Review
- CRISPRi-Linked Multimodule Negative Feedback Loops to Address Winner-Take-All Resource Competition.ACS synthetic biology · 2025Article
- Differential Effects of Snail-KO in Human Breast Epithelial Cells and Human Breast Epithelial × Human Breast Cancer Hybrids.International journal of molecular sciences · 2025Article
- Transition paths across the epithelial-mesenchymal transition landscape are dictated by network logic.Development (Cambridge, England) · 2025Article
- CRISPRi-Linked Multi-Module Negative Feedback Loops to Address Winner-Take-All Resource Competition.bioRxiv : the preprint server for biology · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.PLoS computational biology · 2025Article
- Modeling the dynamics of EMT reveals genes associated with pan-cancer intermediate states and plasticity.NPJ systems biology and applications · 2025Article
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Gene regulatory network inference during cell fate decisions by perturbation strategies.NPJ systems biology and applications · 2025Article
- Fibrotic extracellular matrix preferentially induces a partial Epithelial-Mesenchymal Transition phenotype in a 3-D agent based model of fibrosis.Mathematical biosciences · 2025Article
104 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.