ArticleGastroenterology2012
Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
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Who cites it
169 citing papers in PubMed, 316 citations in OpenAlex.
- Trial
- Mechanically Regulated Secretion: How Physical Forces Instruct the Secretory Pathway and Remodel the Secretome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TERT drives liver tumorigenesis beyond telomere elongation.Life science alliance · 2026Article
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Sustained Notch activation depletes adult neural stem cells and impairs cognitive function.Scientific reports · 2026Article
- Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Strawberry Notch 1 Acts as a Transcriptional Regulator Driving Oncogenic Programs in Liver Carcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multifaceted functions of transcription regulatory factor X6 (RFX6): from pancreatic development to cancer progression.Cancer cell international · 2025Review
- Plastic hepatocyte states limit liver cancer development.Nature communications · 2025Article
- Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.Journal of hepatology · 2025Article
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
- Influencing factors and mechanism of hepatocyte regeneration.Journal of translational medicine · 2025Review
- ACVR2A attenuation impacts lactate production and hyperglycolytic conditions attracting regulatory T cells in hepatocellular carcinoma.Cell reports. Medicine · 2025Article
- NOTCH1 Drives Sexually Dimorphic Immune Responses in Hepatocellular Carcinoma.Cancer discovery · 2025Article
- Sox9 inhibits Activin A to promote biliary maturation and branching morphogenesis.Nature communications · 2025Article
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- A novel vasculogenic mimicry-related nomogram predicts prognosis in hepatocellular carcinoma.Frontiers in genetics · 2025Article
- Re-evaluation of the relationship between PrPc expression and patient prognosis in primary esophageal squamous cell carcinoma and primary hepatocellular carcinoma.Scientific reports · 2024Article
- Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies.Biomolecules · 2024Review
- Effect of Sortilin1 on promoting angiogenesis and systemic metastasis in hepatocellular carcinoma via the Notch signaling pathway and CD133.Cell death & disease · 2024Article
109 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe Notch signaling pathway is activated in leukemia and solid tumors (such as lung cancer), but little is known about its role in liver cancer.
methodsThe intracellular domain of Notch was conditionally expressed in hepatoblasts and their progeny (hepatocytes and cholangiocytes) in mice. This was achieved through Cre expression under the control of an albumin and α-fetoprotein (AFP) enhancer and promoter (AFP-Notch intracellular domain [NICD]). We used comparative functional genomics to integrate transcriptome data from AFP-NICD mice and human hepatocellular carcinoma (HCC) samples (n = 683). A Notch gene signature was generated using the nearest template prediction method.
resultsAFP-NICD mice developed HCC with 100% penetrance when they were 12 months old. Activation of Notch signaling correlated with activation of 3 promoters of insulin-like growth factor 2; these processes appeared to contribute to hepatocarcinogenesis. Comparative functional genomic analysis identified a signature of Notch activation in 30% of HCC samples from patients. These samples had altered expression in Notch pathway genes and activation of insulin-like growth factor signaling, despite a low frequency of mutations in regions of NOTCH1 associated with cancer. Blocking Notch signaling in liver cancer cells with the Notch activation signature using γ-secretase inhibitors or by expressing a dominant negative form of mastermind-like 1 reduced their proliferation in vitro.
conclusionsNotch signaling is activated in human HCC samples and promotes formation of liver tumors in mice. The Notch signature is a biomarker of response to Notch inhibition in vitro.
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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.