ArticleProceedings of the National Academy of Sciences of the United States of America2016
Dynamics inside the cancer cell attractor reveal cell heterogeneity, limits of stability, and escape.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
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- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Understanding the role of toggle genes in chronic lymphocytic leukemia proliferation.NPJ systems biology and applications · 2025Article
- Dynamical systems of fate and form in development.Seminars in cell & developmental biology · 2025Review
- Harnessing the analog computing power of regulatory networks with the Regulatory Network Machine.iScience · 2025Article
- Fokker-Planck diffusion maps of microglial transcriptomes reveal radial differentiation into substates associated with Alzheimer's pathology.Communications biology · 2025Article
- Control of Cellular Differentiation Trajectories for Cancer Reversion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A method for in silico exploration of potential glioblastoma multiforme attractors using single-cell RNA sequencing.Scientific reports · 2024Article
- An attractor state zone precedes neural crest fate in melanoma initiation.bioRxiv : the preprint server for biology · 2024Article
- ClusterMatch aligns single-cell RNA-sequencing data at the multi-scale cluster level via stable matching.Bioinformatics (Oxford, England) · 2024Article
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- Fokker-Planck diffusion maps of multiple single cell microglial transcriptomes reveals radial differentiation into substates associated with Alzheimer's pathology.bioRxiv : the preprint server for biology · 2024Article
- Unveiling the Dynamics behind Glioblastoma Multiforme Single-Cell Data Heterogeneity.International journal of molecular sciences · 2024Article
- Evolution of hierarchy and irreversibility in theoretical cell differentiation model.PNAS nexus · 2024Article
- A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.International journal of molecular sciences · 2023Review
- Cell Population Growth Kinetics in the Presence of Stochastic Heterogeneity of Cell Phenotype.ArXiv · 2023Article
- Article
- Epigenetics as a mediator of plasticity in cancer.Science (New York, N.Y.) · 2023Review
- Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state.Journal of the Royal Society, Interface · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The observed intercellular heterogeneity within a clonal cell population can be mapped as dynamical states clustered around an attractor point in gene expression space, owing to a balance between homeostatic forces and stochastic fluctuations. These dynamics have led to the cancer cell attractor conceptual model, with implications for both carcinogenesis and new therapeutic concepts. Immortalized and malignant EBV-carrying B-cell lines were used to explore this model and characterize the detailed structure of cell attractors. Any subpopulation selected from a population of cells repopulated the whole original basin of attraction within days to weeks. Cells at the basin edges were unstable and prone to apoptosis. Cells continuously changed states within their own attractor, thus driving the repopulation, as shown by fluorescent dye tracing. Perturbations of key regulatory genes induced a jump to a nearby attractor. Using the Fokker-Planck equation, this cell population behavior could be described as two virtual, opposing influences on the cells: one attracting toward the center and the other promoting diffusion in state space (noise). Transcriptome analysis suggests that these forces result from high-dimensional dynamics of the gene regulatory network. We propose that they can be generalized to all cancer cell populations and represent intrinsic behaviors of tumors, offering a previously unidentified characteristic for studying cancer.
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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.