ArticleCancer research2012
Hedgehog signaling blockade delays hepatocarcinogenesis induced by hepatitis B virus X protein.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 66 citations in OpenAlex.
- Role of Oncoviruses in Cancer Progression and Emerging Phytochemical-Based Therapies from Medicinal Plants.Molecular biotechnology · 2026Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2024Review
- The deubiquitinating enzyme USP44 suppresses hepatocellular carcinoma progression by inhibiting Hedgehog signaling and PDL1 expression.Cell death & disease · 2023Article
- Short-chain fatty acids in cancer pathogenesis.Cancer metastasis reviews · 2023Review
- Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers.Cancer metastasis reviews · 2023Review
- Target Therapy for Hepatocellular Carcinoma: Beyond Receptor Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.Biology · 2022Review
- H5N1 infection impairs the alveolar epithelial barrier through intercellular junction proteins via Itch-mediated proteasomal degradation.Communications biology · 2022Article
- Utilizing Gut Microbiota to Improve Hepatobiliary Tumor Treatments: Recent Advances.Frontiers in oncology · 2022Review
- The Emerging Role of Hedgehog Signaling in Viral Infections.Frontiers in microbiology · 2022Review
- Short chain fatty acids delay the development of hepatocellular carcinoma in HBx transgenic mice.Neoplasia (New York, N.Y.) · 2021Article
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
- Article
- Review
- Cancer Cell-Derived Exosomes Promote HCC Tumorigenesis Through Hedgehog Pathway.Frontiers in oncology · 2021Article
- When Viruses Cross Developmental Pathways.Frontiers in cell and developmental biology · 2021Review
- The Role of Smoothened in Cancer.International journal of molecular sciences · 2020Review
- Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies.Cells · 2020Review
- Review
- Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus, experiments were designed to test the hypothesis that HBx promotes HCC via activation of Hh signaling. HBx expression correlated with an upregulation of Hh markers in human liver cancer cell lines, in liver samples from HBV infected patients with HCC, and in the livers of HBx transgenic mice (HBxTg) that develop hepatitis, steatosis, and dysplasia, culminating in the appearance of HCC. The findings in human samples provide clinical validation for the in vitro results and those in the HBxTg. Blockade of Hh signaling inhibited HBx stimulation of cell migration, anchorage-independent growth, tumor development in HBxTg, and xenograft growth in nude mice. Results suggest that the ability of HBx to promote cancer is at least partially dependent upon the activation of the Hh pathway. This study provides biologic evidence for the role of Hh signaling in the pathogenesis of HBV-mediated HCC and suggests cause and effect for the first time. The observation that inhibition of Hh signaling partially blocked the ability of HBx to promote growth and migration in vitro and tumorigenesis in two animal models implies that Hh signaling may represent an "oncogene addiction" pathway for HBV-associated HCC. This work could be central to designing specific treatments that target early development and progression of HBx-mediated 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.