ArticleeLife2021
Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Amino Acids Frequency and Interaction Trends: Comprehensive Analysis of Experimentally Validated Viral Antigen-Antibody Complexes.Molecular biotechnology · 2026Article
- Fluctuation structure predicts genome-wide perturbation outcomes.Research square · 2025Article
- Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks.Journal of the Royal Society, Interface · 2025Article
- Fluctuation structure predicts genome-wide perturbation outcomes.bioRxiv : the preprint server for biology · 2025Article
- Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks.iScience · 2025Article
- Operating principles of interconnected feedback loops driving cell fate transitions.NPJ systems biology and applications · 2025Article
- Study protocol for design of a personalized dietary supplement based on the gut microbiota of Alzheimer's patients and evaluation of its effects in a pilot randomized controlled trial.Frontiers in nutrition · 2025Article
- Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma.Cancer biology & therapy · 2024Article
- Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.NPJ systems biology and applications · 2024Article
- Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.iScience · 2024Article
- Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.Science advances · 2024Article
- Redox signalling regulates breast cancer metastasis via phenotypic and metabolic reprogramming due to p63 activation by HIF1α.British journal of cancer · 2024Article
- Proneural-mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in glioblastoma.iScience · 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
- Toward a systems-level probing of tumor clonality.iScience · 2023Review
- Mapping Spatiotemporal Heterogeneity in Tumor Profiles by Integrating High-Throughput Imaging and Omics Analysis.ACS omega · 2023Review
- Article
- Minimal frustration underlies the usefulness of incomplete regulatory network models in biology.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Emergent dynamics of underlying regulatory network links EMT and androgen receptor-dependent resistance in prostate cancer.Computational and structural biotechnology journal · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Phenotypic (non-genetic) heterogeneity has significant implications for the development and evolution of organs, organisms, and populations. Recent observations in multiple cancers have unraveled the role of phenotypic heterogeneity in driving metastasis and therapy recalcitrance. However, the origins of such phenotypic heterogeneity are poorly understood in most cancers. Here, we investigate a regulatory network underlying phenotypic heterogeneity in small cell lung cancer, a devastating disease with no molecular targeted therapy. Discrete and continuous dynamical simulations of this network reveal its multistable behavior that can explain co-existence of four experimentally observed phenotypes. Analysis of the network topology uncovers that multistability emerges from two teams of players that mutually inhibit each other, but members of a team activate one another, forming a 'toggle switch' between the two teams. Deciphering these topological signatures in cancer-related regulatory networks can unravel their 'latent' design principles and offer a rational approach to characterize phenotypic heterogeneity in a tumor.
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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 Socratic graph.