ArticleProceedings of the National Academy of Sciences of the United States of America2013
MicroRNA-based regulation of epithelial-hybrid-mesenchymal fate determination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 304 papers.
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Who cites it
304 citing papers in PubMed.
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Zeb1 Is a Determinant of EMT in Human MDA-MB-231 Breast Cancer Cells and M13-MDA231 Tumor Hybrids.International journal of molecular sciences · 2026Article
- Learning stochasticity via a nonparametric approach to state-dependent noise estimation.Nature communications · 2026Article
- Mechanisms Underlying the Coordination of EMT and Glycolysis Mediated by Hypoxia and Glucose.Current issues in molecular biology · 2026Article
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
- Review
- Adherent-to-suspension transition modulates circulating tumor cell dynamics and metastatic potential in melanoma.Molecules and cells · 2026Article
- EMTscore infers divergent EMT pathways from omics data and enables rapid screening for EMT-associated gene sets.Bioinformatics (Oxford, England) · 2026Article
- Design principles for robust multistability in coupled feedforward-feedback regulatory circuits.NPJ systems biology and applications · 2026Article
- Rewiring miR-22/SNAI1 via CRISPR-based edge editing destabilizes the epithelial phenotype.NPJ systems biology and applications · 2026Article
- Understanding and Exploiting Biological Mechanisms of Radiosensitization Using High Atomic Mass Nanomaterials.Nanomaterials (Basel, Switzerland) · 2026Review
- Review
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- Gain of function p53 mutant R273H confers distinct methylation profiles and consequent YAP/TAZ signaling mediated activation of partial or full EMT states to colon tumours.Epigenetics & chromatin · 2025Article
- Core microRNAs regulate neural crest delamination and condensation in the developing trigeminal ganglion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A computational approach for perturbation-induced EMT transitions.NPJ systems biology and applications · 2025Article
- Wnt/ERK/CDK4/6 activation in the partial EMT state coordinates mammary cancer stemness with self-renewal and inhibition of differentiation.British journal of cancer · 2025Article
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Differential Effects of Snail-KO in Human Breast Epithelial Cells and Human Breast Epithelial × Human Breast Cancer Hybrids.International journal of molecular sciences · 2025Article
244 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forward and backward transitions between epithelial and mesenchymal phenotypes play crucial roles in embryonic development and tissue repair. Aberrantly regulated transitions are also a hallmark of cancer metastasis. The genetic network that regulates these transitions appears to allow for the existence of a hybrid phenotype (epithelial/mesenchymal). Hybrid cells are endowed with mixed epithelial and mesenchymal characteristics, enabling specialized capabilities such as collective cell migration. Cell-fate determination between the three phenotypes is in fact regulated by a circuit composed of two highly interconnected chimeric modules--the miR-34/SNAIL and the miR-200/ZEB mutual-inhibition feedback circuits. Here, we used detailed modeling of microRNA-based regulation to study this core unit. More specifically, we investigated the functions of the two isolated modules and subsequently of the combined unit when the two modules are integrated into the full regulatory circuit. We found that miR-200/ZEB forms a tristable circuit that acts as a ternary switch, driven by miR-34/SNAIL, that is a monostable module that acts as a noise-buffering integrator of internal and external signals. We propose to associate the three stable states--(1,0), (high miR-200)/(low ZEB); (0,1), (low miR-200)/(high ZEB); and (1/2,1/2), (medium miR-200)/(medium ZEB)--with the epithelial, mesenchymal, and hybrid phenotypes, respectively. Our (1/2,1/2) state hypothesis is consistent with recent experimental studies (e.g., ZEB expression measurements in collectively migrating cells) and explains the lack of observed mesenchymal-to-hybrid transitions in metastatic cells and in induced pluripotent stem cells. Testable predictions of dynamic gene expression during complete and partial transitions are presented.
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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.