ArticleCancer research2014
Network modeling of TGFβ signaling in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint sonic hedgehog and Wnt pathway activation.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 253 citations in OpenAlex.
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- Translating Fibrosis to Malignancy: Biomarkers and Therapeutic Opportunities in Liver Fibrosis and Hepatocellular Carcinoma.Medical sciences (Basel, Switzerland) · 2026Review
- A computational approach for perturbation-induced EMT transitions.NPJ systems biology and applications · 2025Article
- Mendelian randomization and mediation analysis reveal the role of immune cells in the pathways between inflammatory factors and glioblastoma.The Journal of international medical research · 2025Article
- Qingrehuoxue formula enhances anti-PD-1 immunotherapy in NSCLC by remodeling the tumor immune microenvironment via TREM2 signaling.BMC complementary medicine and therapies · 2025Article
- Mapping the attractor landscape of Boolean networks with biobalm.Bioinformatics (Oxford, England) · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Complex networks interactions between bioactive compounds and adipose tissue vis-à-vis insulin resistance.Frontiers in endocrinology · 2025Article
- A Multicellular Mechanochemical Model to Investigate Tumor Microenvironment Remodeling and Pre-Metastatic Niche Formation.Cellular and molecular bioengineering · 2024Article
- Energy Landscape Reveals the Underlying Mechanism of Cancer-Adipose Conversion in Gene Network Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility.bioRxiv : the preprint server for biology · 2024Article
- A Boolean model explains phenotypic plasticity changes underlying hepatic cancer stem cells emergence.NPJ systems biology and applications · 2024Article
- Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma.Scientific reports · 2024Article
- Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.NPJ systems biology and applications · 2024Article
- Decoding the principle of cell-fate determination for its reverse control.NPJ systems biology and applications · 2024Article
- Cell reprogramming design by transfer learning of functional transcriptional networks.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to leave the primary tumor site, invade surrounding tissue, and establish distant metastases. A hallmark of EMT is the loss of E-cadherin expression, and one major signal for the induction of EMT is TGFβ, which is dysregulated in up to 40% of hepatocellular carcinoma (HCC). We have constructed an EMT network of 70 nodes and 135 edges by integrating the signaling pathways involved in developmental EMT and known dysregulations in invasive HCC. We then used discrete dynamic modeling to understand the dynamics of the EMT network driven by TGFβ. Our network model recapitulates known dysregulations during the induction of EMT and predicts the activation of the Wnt and Sonic hedgehog (SHH) signaling pathways during this process. We show, across multiple murine (P2E and P2M) and human HCC cell lines (Huh7, PLC/PRF/5, HLE, and HLF), that the TGFβ signaling axis is a conserved driver of mesenchymal phenotype HCC and confirm that Wnt and SHH signaling are induced in these cell lines. Furthermore, we identify by network analysis eight regulatory feedback motifs that stabilize the EMT process and show that these motifs involve cross-talk among multiple major pathways. Our model will be useful in identifying potential therapeutic targets for the suppression of EMT, invasion, and metastasis in HCC.
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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.