ArticleNature cell biology2012
Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin.
Article in Nature cell biology, 2012. 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 146 papers, 1 of them a synthesis that pooled it.
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
146 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of gene expression profiles identifies differential biomarkers for hepatocellular carcinoma and cholangiocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Pooled it
- Article
- Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma.Nature communications · 2026Article
- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- Histone Deacetylase Inhibitors Promote the Anticancer Activity of Cisplatin: Mechanisms and Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.Cancers · 2025Review
- Suppressing SENP1 inhibits esophageal squamous carcinoma cell growth via SIRT6 SUMOylation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Network pharmacology integrated with molecular docking and experimental validation elucidates the therapeutic potential ofFrontiers in oncology · 2025Article
- Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect.Bioactive materials · 2024Article
- Sirt6 ablation in the liver causes fatty liver that increases cancer risky by upregulating Serpina12.EMBO reports · 2024Article
- Article
- SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation.Aging cell · 2024Article
- ZBTB7B is a permissive regulator of hepatocellular carcinoma initiation by repressing c-Jun expression and function.Cell death & disease · 2024Article
- The Role of Sirtuin 6 in the Deacetylation of Histone Proteins as a Factor in the Progression of Neoplastic Disease.International journal of molecular sciences · 2023Review
- Targeting the deacetylase SIRT6 unveils spliceosome deregulation as exploitable vulnerability for aggressive myeloma.Blood advances · 2023Article
- Cellular senescence-related long noncoding ribonucleic acids: Predicting prognosis in hepatocellular carcinoma.Cancer reports (Hoboken, N.J.) · 2023Article
- Review
- Dihydroartemisinin imposes positive and negative regulation on Treg and plasma cells via direct interaction and activation of c-Fos.Communications biology · 2023Article
- SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.Aging and disease · 2022Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding stage-dependent oncogenic mechanisms is critical to develop not only targeted therapies, but also diagnostic markers and preventive strategies. The mechanisms acting during cancer initiation remain elusive, largely owing to a lack of suitable animal models and limited availability of human precancerous lesions. Here we show using genetic mouse models specific for liver cancer initiation, that survival of initiated cancer cells is controlled by c-Jun, independently of p53, through suppressing c-Fos-mediated apoptosis. Mechanistically, c-Fos induces SIRT6 transcription, which represses survivin by reducing histone H3K9 acetylation and NF-κB activation. Importantly, increasing the level of SIRT6 or targeting the anti-apoptotic activity of survivin at the initiation stage markedly impairs cancer development. Moreover, in human dysplastic liver nodules, but not in malignant tumours, a specific expression pattern with increased c-Jun-survivin and attenuated c-Fos-SIRT6 levels was identified. These results reveal a regulatory network connecting stress response and histone modification in liver tumour initiation, which could be targeted to prevent liver tumorigenesis.
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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.