ArticleThe Journal of clinical investigation2015
Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 211 citations in OpenAlex.
- HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.The Journal of clinical investigation · 2018Trial
- Hepatic stellate cell subpopulations in human MASLD-related hepatocellular carcinoma upregulate YAP via geranylgeranyl pyrophosphate.Hepatology communications · 2026Article
- Late-stage dedifferentiation and epigenetic memory of cancer stem cells in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Cell-free DNA fragmentomes for noninvasive detection of liver cirrhosis and other diseases.Science translational medicine · 2026Article
- Oncogenic function and transcriptional dynamics of MYCN in liver tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Integrative Single-Cell and Spatial Transcriptomic Analysis Reveals MAIT Cell Dysfunction in Relapsed HCC.Journal of hepatocellular carcinoma · 2026Article
- Early Recurrent Hepatocellular Carcinoma with CK19 Positive Receiving Transarterial Chemoembolization After Surgical Resection: A Novel Risk Model Study.Journal of hepatocellular carcinoma · 2026Article
- Osteopontin: a central hub in the pathogenesis and therapeutic intervention of liver disease.Annals of medicine · 2025Review
- MEF2D-expressing cancer precursors reprogram tissue-resident macrophages to support liver tumorigenesis.Nature cancer · 2025Article
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- The rise of RAS: how gradual oncogene activation shapes the OIS spectrum.Genes & development · 2025Review
- DNA Methylation Concurrence, Independent of DNA Methylation Ratios, Is Associated with Chromatin Accessibility and 3D Genome Architecture.International journal of molecular sciences · 2025Article
- Identification of matrix stiffness-related molecular subtypes in HCC via integrating multi-omics analysis and machine learning algorithms.Journal of translational medicine · 2025Article
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- Silibinin-Conjugated Galactose Dendrimers for Targeted Treatment of Hepatocellular Carcinoma.ACS applied materials & interfaces · 2025Article
- Current status and new directions for hepatocellular carcinoma diagnosis.Liver research (Beijing, China) · 2024Review
- Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.Clinical and translational medicine · 2024Article
- Aberrant differentiation and proliferation of hepatocytes in chronic liver injury and liver tumors.Pathology international · 2024Review
- Cellular Origins and Lineage Plasticity in Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
In many organs, including the intestine and skin, cancers originate from cells of the stem or progenitor compartment. Despite its nomenclature, the cellular origin of hepatocellular carcinoma (HCC) remains elusive. In contrast to most organs, the liver lacks a defined stem cell population for organ maintenance. Previous studies suggest that both hepatocytes and facultative progenitor cells within the biliary compartment are capable of generating HCC. As HCCs with a progenitor signature carry a worse prognosis, understanding the origin of HCC is of clinical relevance. Here, we used complementary fate-tracing approaches to label the progenitor/biliary compartment and hepatocytes in murine hepatocarcinogenesis. In genotoxic and genetic models, HCCs arose exclusively from hepatocytes but never from the progenitor/biliary compartment. Cytokeratin 19-, A6- and α-fetoprotein-positive cells within tumors were hepatocyte derived. In summary, hepatocytes represent the cell of origin for HCC in mice, and a progenitor signature does not reflect progenitor origin, but dedifferentiation of hepatocyte-derived tumor cells.
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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.