ArticleThe Journal of clinical investigation2010
Elimination of C/EBPalpha through the ubiquitin-proteasome system promotes the development of liver cancer in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Transcriptional control of a stem cell factor nucleostemin in liver regeneration and aging.PloS one · 2024Article
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- Review
- Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner.Cell death discovery · 2022Article
- Second Generation Small Molecule Inhibitors of Gankyrin for the Treatment of Pediatric Liver Cancer.Cancers · 2022Article
- Small Molecule Cjoc42 Improves Chemo-Sensitivity and Increases Levels of Tumor Suppressor Proteins in Hepatoblastoma Cells and in Mice by Inhibiting Oncogene Gankyrin.Frontiers in pharmacology · 2021Article
- Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair.Developmental cell · 2020Article
- The "Janus" Role of C/EBPs Family Members in Cancer Progression.International journal of molecular sciences · 2020Review
- Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease.Hepatology communications · 2019Article
- Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.Cell reports · 2018Article
- C/EBPα-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer.Hepatology (Baltimore, Md.) · 2018Article
- Monocyte-Specific Knockout of C/ebpα Results in Osteopetrosis Phenotype, Blocks Bone Loss in Ovariectomized Mice, and Reveals an Important Function of C/ebpα in Osteoclast Differentiation and Function.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- C/ebpα controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1.The Journal of pathology · 2018Article
- Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway.Aging cell · 2018Article
- PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma.Communications biology · 2018Article
- Gankyrin Promotes Tumor-Suppressor Protein Degradation to Drive Hepatocyte Proliferation.Cellular and molecular gastroenterology and hepatology · 2018Article
- Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα.Frontiers in pharmacology · 2018Article
- Review
- RNA Binding Protein CUGBP1 Inhibits Liver Cancer in a Phosphorylation-Dependent Manner.Molecular and cellular biology · 2017Article
- FXR-Gankyrin axis is involved in development of pediatric liver cancer.Carcinogenesis · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Despite significant advancements in our understanding of cancer development, the molecular mechanisms that underlie the formation of liver cancer remain largely unknown. C/EBPalpha is a transcription factor that regulates liver quiescence. Phosphorylation of C/EBPalpha at serine 193 (S193-ph) is upregulated in older mice and is thought to contribute to age-associated liver dysfunction. Because development of liver tumors is associated with increasing age, we investigated the role of S193-ph in the development of liver cancer using knockin mice expressing a phospho-mimetic aspartic acid residue in place of serine at position 193 (S193D) of C/EBPalpha. The S193D isoform of C/EBPalpha was able to completely inhibit liver proliferation in vivo after partial hepatectomy. However, treatment of these mice with diethylnitrosamine/phenobarbital (DEN/PB), which induces formation of liver cancer, actually resulted in earlier development of liver tumors. DEN/PB treatment was associated with specific degradation of both the S193-ph and S193D isoforms of C/EBPalpha through activation of the ubiquitinproteasome system (UPS). The mechanism of UPS-mediated elimination of C/EBPalpha during carcinogenesis involved elevated levels of gankyrin, a protein that was found to interact with the S193-ph isoform of C/EBPalpha and target it for UPS-mediated degradation. This study identifies a molecular mechanism that supports the development of liver cancer in older mice and potential therapeutic targets for the prevention of liver cancer.
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