ArticleHepatology (Baltimore, Md.)2011
Carcinogen-induced hepatic tumors in KLF6+/- mice recapitulate aggressive human hepatocellular carcinoma associated with p53 pathway deregulation.
Article in Hepatology (Baltimore, Md.), 2011. 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 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed, 46 citations in OpenAlex.
- Syndecan-1 Promotes Alveolar Type 2 Epithelial Cell Senescence during Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Murine double minute 2 (MDM2) as an appealing target for natural products in cancer treatment.Molecular biology reports · 2026Review
- BTF3 affects hepatocellular carcinoma progression by transcriptionally upregulating PDCD2L and inactivating p53 signaling.Molecular medicine (Cambridge, Mass.) · 2024Article
- Prognosis-oriented molecular subtypes of retroperitoneal liposarcoma.Clinical and translational medicine · 2024Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- Role of p53 suppression in the pathogenesis of hepatocellular carcinoma.World journal of gastrointestinal pathophysiology · 2023Review
- LncRNA KASRT Serves as a Potential Treatment Target by Regulating SRSF1-Related KLF6 Alternative Splicing and the P21/CCND1 Pathway in Osteosarcoma: AnFrontiers in oncology · 2021Article
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Role of Non-Coding RNAs in the Progression of Liver Cancer: Evidence from Experimental Models.Cancers · 2019Review
- Effects of Ferroportin-Mediated Iron Depletion in Cells Representative of Different Histological Subtypes of Prostate Cancer.Antioxidants & redox signaling · 2019Article
- Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma.World journal of hepatology · 2018Review
- Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury.Scientific reports · 2017Article
- Selecting optimal combinations of transcription factors to promote axon regeneration: Why mechanisms matter.Neuroscience letters · 2017Review
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- p53 and RAD9, the DNA Damage Response, and Regulation of Transcription Networks.Radiation research · 2017Review
- KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities.International journal of medical sciences · 2017Article
- Kruppel-like factor 6 suppresses growth and invasion of hepatocellular carcinoma cells in vitro and in vivo.International journal of immunopathology and pharmacology · 2016Article
- A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination.Oncogene · 2016Article
- Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes.World journal of gastroenterology · 2016Review
- Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research.Quantitative imaging in medicine and surgery · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
unlabelledInactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental hepatocarcinogenesis in vivo. In patients with surgically resected HCC, reduced tumor expression of KLF6 was associated with decreased survival. Consistent with its role as a tumor suppressor, KLF6+/- mice developed significantly more tumors in response to the chemical carcinogen diethyl nitrosamine (DEN) than wild-type animals. Gene expression signatures in both surrounding tissue and tumors of KLF6+/- mice closely recapitulated those associated with aggressive human HCCs. Expression microarray profiling also revealed an increase in Mdm2 mRNA in tumors from KLF6+/- compared with KLF6+/+ mice, which was validated by way of quantitative real-time polymerase chain reaction and western blot analysis in both human HCC and DEN-induced murine tumors. Moreover, chromatin immunoprecipitation and cotransfection assays established the P2 intronic promoter of Mdm2 as a bona fide transcriptional target repressed by KLF6. Whereas KLF6 overexpression in HCC cell lines and primary hepatocytes led to reduced MDM2 levels and increased p53 protein and transcriptional activity, reduction in KLF6 by small interfering RNA led to increased MDM2 and reduced p53.
conclusionOur findings indicate that KLF6 deficiency contributes significantly to the carcinogenic milieu in human and murine HCC and uncover a novel tumor suppressor activity of KLF6 in HCC by linking its transcriptional repression of Mdm2 to stabilizing p53.
Indexed as
Identifiers
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.