ArticleCell death & disease2021
Loss of Numb promotes hepatic progenitor expansion and intrahepatic cholangiocarcinoma by enhancing Notch signaling.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Endocytic Control of Cell-Autonomous and Non-Cell-Autonomous Functions of p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synergistic amelioration of cholestatic liver fibrosis by combined total astragalus saponins and AAV8.Frontiers in pharmacology · 2026Article
- Notch signaling in liver diseases: mechanistic insights and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Loss of NUMB promotes hepatomegaly and hepatocellular carcinoma through the AKT/glycogen/hippo signaling.Oncogene · 2025Article
- The CRL7Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NOTCH Signaling Networks in Perivascular Adipose Tissue.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- HPLC-HRMS/MS and anti-inflammatory effects of bunya pine resin through multifaceted pathway modulation: NUMB/NOTCH1/HES1/mTOR/ PI3K/HMGB1 signaling cascades.Inflammopharmacology · 2025Article
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.Nature communications · 2024Article
- NUMB attenuates posttraumatic osteoarthritis by inhibiting BTRC and inactivating the NF-κB pathway.Journal of orthopaedic surgery and research · 2024Article
- Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.Molecular cancer · 2024Article
- Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Dissecting the tumor ecosystem of liver cancers in the single-cell era.Hepatology communications · 2023Review
- Review
- A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Numb, a stem cell fate determinant, acts as a tumor suppressor and is closely related to a wide variety of malignancies. Intrahepatic cholangiocarcinoma (iCCA) originates from hepatic progenitors (HPCs); however, the role of Numb in HPC malignant transformation and iCCA development is still unclear. A retrospective cohort study indicated that Numb was frequently decreased in tumor tissues and suggests poor prognosis in iCCA patients. Consistently, in a chemically induced iCCA mouse model, Numb was downregulated in tumor cells compared to normal cholangiocytes. In diet-induced chronic liver injury mouse models, Numb ablation significantly promoted histological impairment, HPC expansion, and tumorigenesis. Similarly, Numb silencing in cultured iCCA cells enhanced cell spheroid growth, invasion, metastasis, and the expression of stem cell markers. Mechanistically, Numb was found to bind to the Notch intracellular domain (NICD), and Numb ablation promoted Notch signaling; this effect was reversed when Notch signaling was blocked by γ-secretase inhibitor treatment. Our results suggested that loss of Numb plays an important role in promoting HPC expansion, HPC malignant transformation, and, ultimately, iCCA development in chronically injured livers. Therapies targeting suppressed Numb are promising for the treatment of iCCA.
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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.