ArticleJournal of clinical medicine2020
Hybrid E/M Phenotype(s) and Stemness: A Mechanistic Connection Embedded in Network Topology.
Article in Journal of clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Multiple distinct metastatic cell states are induced by epithelial-mesenchymal plasticity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Circulating Tumor Cells for the Monitoring of Lung Cancer Therapies.International journal of molecular sciences · 2025Review
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids.iScience · 2025Article
- Re-epithelialization of cancer cells increases autophagy and DNA damage: Implications for breast cancer dormancy and relapse.Science signaling · 2025Article
- Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks.iScience · 2025Article
- Review
- Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma.Cancer biology & therapy · 2024Article
- Phenotypic Plasticity and Cancer: A System Biology Perspective.Journal of clinical medicine · 2024Review
- Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.iScience · 2024Article
- Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma.Bioactive materials · 2024Article
- A systems-level analysis of the mutually antagonistic roles of RKIP and BACH1 in dynamics of cancer cell plasticity.Journal of the Royal Society, Interface · 2023Article
- Zinc Finger 521 Modulates the Nrf2-Notch Signaling Pathway in Human Ovarian Carcinoma.International journal of molecular sciences · 2023Article
- Genomic and transcriptomic profiling reveal molecular characteristics of parathyroid carcinoma.Experimental & molecular medicine · 2023Article
- Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype.Molecules and cells · 2023Review
- The ELF3 transcription factor is associated with an epithelial phenotype and represses epithelial-mesenchymal transition.Journal of biological engineering · 2023Article
- Loss of CD24 promotes radiation‑ and chemo‑resistance by inducing stemness properties associated with a hybrid E/M state in breast cancer cells.Oncology reports · 2023Article
- Targeting Breast Cancer Stem Cells.International journal of biological sciences · 2023Review
- Interconnected high-dimensional landscapes of epithelial-mesenchymal plasticity and stemness in cancer.Clinical & experimental metastasis · 2022Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Metastasis remains an unsolved clinical challenge. Two crucial features of metastasizing cancer cells are (a) their ability to dynamically move along the epithelial-hybrid-mesenchymal spectrum and (b) their tumor initiation potential or stemness. With increasing functional characterization of hybrid epithelial/mesenchymal (E/M) phenotypes along the spectrum, recent in vitro and in vivo studies have suggested an increasing association of hybrid E/M phenotypes with stemness. However, the mechanistic underpinnings enabling this association remain unclear. Here, we develop a mechanism-based mathematical modeling framework that interrogates the emergent nonlinear dynamics of the coupled network modules regulating E/M plasticity (miR-200/ZEB) and stemness (LIN28/let-7). Simulating the dynamics of this coupled network across a large ensemble of parameter sets, we observe that hybrid E/M phenotype(s) are more likely to acquire stemness relative to "pure" epithelial or mesenchymal states. We also integrate multiple "phenotypic stability factors" (PSFs) that have been shown to stabilize hybrid E/M phenotypes both in silico and in vitro-such as OVOL1/2, GRHL2, and NRF2-with this network, and demonstrate that the enrichment of hybrid E/M phenotype(s) with stemness is largely conserved in the presence of these PSFs. Thus, our results offer mechanistic insights into recent experimental observations of hybrid E/M phenotype(s) that are essential for tumor initiation and highlight how this feature is embedded in the underlying topology of interconnected EMT (Epithelial-Mesenchymal Transition) and stemness networks.
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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.