ArticleOncotarget2018
A mechanism-based computational model to capture the interconnections among epithelial-mesenchymal transition, cancer stem cells and Notch-Jagged signaling.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging.Stem cell research & therapy · 2025Article
- Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.International journal of molecular sciences · 2025Review
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- Spatial and Temporal Relationship between Epithelial-Mesenchymal Transition (EMT) and Stem Cells in Cancer.Clinical chemistry · 2024Article
- Reconstructing growth and dynamic trajectories from single-cell transcriptomics data.Nature machine intelligence · 2024Article
- Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer.iScience · 2023Article
- Cancer Stemness/Epithelial-Mesenchymal Transition Axis Influences Metastasis and Castration Resistance in Prostate Cancer: Potential Therapeutic Target.International journal of molecular sciences · 2022Review
- Chemokines and cytokines: Axis and allies in prostate cancer pathogenesis.Seminars in cancer biology · 2022Review
- Growth dynamics of breast cancer stem cells: effects of self-feedback and EMT mechanisms.Theory in biosciences = Theorie in den Biowissenschaften · 2022Article
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Transcriptomic-Based Quantification of the Epithelial-Hybrid-Mesenchymal Spectrum across Biological Contexts.Biomolecules · 2021Article
- Review
- Review
- Article
- Deciphering the molecular mechanism of the cancer formation by chromosome structural dynamics.PLoS computational biology · 2021Article
- Epithelial-to-Mesenchymal Transition in the Light of Plasticity and Hybrid E/M States.Journal of clinical medicine · 2021Review
- EMT-associated microRNAs and their roles in cancer stemness and drug resistance.Cancer communications (London, England) · 2021Review
- Multi-Stability and Consequent Phenotypic Plasticity in AMPK-Akt Double Negative Feedback Loop in Cancer Cells.Journal of clinical medicine · 2021Article
- Communication Between Epithelial-Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression.Frontiers in oncology · 2021Review
- Regulation of Partial and Reversible Endothelial-to-Mesenchymal Transition in Angiogenesis.Frontiers in cell and developmental biology · 2021Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) and cancer stem cell (CSCs) formation are two fundamental and well-studied processes contributing to cancer metastasis and tumor relapse. Cells can undergo a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype or a complete EMT to attain a mesenchymal one. Similarly, cells can reversibly gain or lose 'stemness'. This plasticity in cell states is modulated by signaling pathways such as Notch. However, the interconnections among the cell states enabled by EMT, CSCs and Notch signaling remain elusive. Here, we devise a computational model to investigate the coupling among the core decision-making circuits for EMT, CSCs and Notch. Our model predicts that hybrid E/M cells are most likely to associate with stem-like traits and enhanced Notch-Jagged signaling - a pathway implicated in therapeutic resistance. Further, we show that the position of the 'stemness window' on the 'EMT axis' is varied by altering the coupling strength between EMT and CSC circuits, and/or modulating Notch signaling. Finally, we analyze the gene expression profile of CSCs from several cancer types and observe a heterogeneous distribution along the 'EMT axis', suggesting that different subsets of CSCs may exist with varying phenotypes along the epithelial-mesenchymal axis. We further investigate therapeutic perturbations such as treatment with metformin, a drug associated with decreased cancer incidence and increased lifespan of patients. Our mechanism-based model explains how metformin can both inhibit EMT and blunt the aggressive potential of CSCs simultaneously, by driving the cells out of a hybrid E/M stem-like state with enhanced Notch-Jagged signaling.
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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.