ArticleProceedings of the National Academy of Sciences of the United States of America2019
Toward understanding cancer stem cell heterogeneity in the tumor microenvironment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 2 of them syntheses that pooled it.
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Who cites it
175 citing papers in PubMed, 2 syntheses or guidelines pooled it, 311 citations in OpenAlex.
- Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.Cells, tissues, organs · 2021Pooled it
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Spatial modelling of NOTCH signalling predicts tuneable dynamic heterogeneity in endothelia.NPJ systems biology and applications · 2026Article
- Decoding cellular population dynamics through mechanistic modelling and statistical data analysis.NPJ systems biology and applications · 2026Review
- Integrative QSP Modeling of Cancer Stem Cells in Triple-Negative Breast Cancer: Impacts on Tumor Immunity and Response to Immune Checkpoint Inhibitors.CPT: pharmacometrics & systems pharmacology · 2026Article
- The stem cell atlas of lung adenocarcinoma: A stemness blueprint for prognosis and immunotherapy success.Translational oncology · 2026Article
- Natural product derived phytochemicals as modulators of cancer stemness and drug resistance.Frontiers in oncology · 2026Review
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment.Frontiers in immunology · 2026Review
- Targeting the SMAD3/CISD2 axis suppresses bladder cancer progression by promoting ferroptosis in mesenchymal-like bladder cancer cells.Cell death & disease · 2025Article
- Identification of key genes in pancreatic ductal adenocarcinoma with biologically informed deep neural network.Journal of gastrointestinal oncology · 2025Article
- MMP9 shapes cell mechanics to enable collective invasion in cancer.NPJ systems biology and applications · 2025Article
- Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.Cancer cell international · 2025Review
- Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging.Stem cell research & therapy · 2025Article
- Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Metabolic reprogramming and functional crosstalk within the tumor microenvironment (TME) and A Multi-omics anticancer approach.Medical oncology (Northwood, London, England) · 2025Review
- Personalized cancer treatment strategies incorporating irreversible and reversible drug resistance mechanisms.NPJ systems biology and applications · 2025Article
- Heterogeneous protein dynamics links to mitochondrial activity, glucose transporter, and ALDH cancer stem cell properties.BMC cancer · 2025Article
- HES1 in cancer: a key player in tumorigenesis and its prognostic significance.Molecular genetics and genomics : MGG · 2025Review
115 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are two paramount processes driving tumor progression, therapy resistance, and cancer metastasis. Recent experiments show that cells with varying EMT and CSC phenotypes are spatially segregated in the primary tumor. The underlying mechanisms generating such spatiotemporal dynamics in the tumor microenvironment, however, remain largely unexplored. Here, we show through a mechanism-based dynamical model that the diffusion of EMT-inducing signals such as TGF-β, together with noncell autonomous control of EMT and CSC decision making via the Notch signaling pathway, can explain experimentally observed disparate localization of subsets of CSCs with varying EMT phenotypes in the tumor. Our simulations show that the more mesenchymal CSCs lie at the invasive edge, while the hybrid epithelial/mesenchymal (E/M) CSCs reside in the tumor interior. Further, motivated by the role of Notch-Jagged signaling in mediating EMT and stemness, we investigated the microenvironmental factors that promote Notch-Jagged signaling. We show that many inflammatory cytokines such as IL-6 that can promote Notch-Jagged signaling can (
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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.