ArticleNature2018
Necroptosis microenvironment directs lineage commitment in liver cancer.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 255 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
255 citing papers in PubMed, 420 citations in OpenAlex.
- A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma.Cancer discovery · 2022Trial
- Multimodal Imaging under Artificial Intelligence Algorithm for the Diagnosis of Liver Cancer and Its Relationship with Expressions of EZH2 and p57.Computational intelligence and neuroscience · 2022Trial
- Progressive suppression of regulated cell death defines terminal macrophage states in liver cirrhosis.Annals of medicine · 2026Article
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Dying cells as architects of the stem cell niche: a conserved mechanism driving tissue regeneration and tumor therapy resistance.Cell communication and signaling : CCS · 2026Review
- Dynamic Decoration of DNA Scaffolds for High-Resolution Cancer Cell Subtyping.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Uncoupling Metastasis and Epithelial-to-Mesenchymal Transition in sgP19/kRAS-Driven Spontaneous Metastatic Liver Tumor Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chronic stress drives liver cancer by impairing the hepatic kynurenine pathway and immune surveillance.Nature metabolism · 2026Article
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytes.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Review
- Neutrophil depletion dampens inflammation and enhances CD8Translational cancer research · 2025Article
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting tumor-intrinsic BCL9 reverses immunotherapy resistance by eliciting macrophage-mediated phagocytosis and antigen presentation.Nature communications · 2025Article
- Targeting immunosuppressive macrophages by CSRP2-regulated CCL28 signaling sensitizes hepatocellular carcinoma to lenvatinib.Journal for immunotherapy of cancer · 2025Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
195 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
24 authors at 8 institutions in 5 countries.
Funding
Abstract
Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans. Together, our results provide insight into lineage commitment in liver tumorigenesis, and explain molecularly why common liver-damaging risk factors can lead to either HCC or ICC.
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What OpenQuestion holds
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.