ArticleProceedings of the National Academy of Sciences of the United States of America2018
Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 99 citations in OpenAlex.
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- NEDD4 regulates VEGF signaling and mTOR to promote angiogenesis and the cell cycle in steroid‑induced osteonecrosis of the femoral head.Molecular medicine reports · 2026Article
- Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe.Scientific reports · 2025Article
- The Impact of Proinflammatory M1 Macrophages on the Proliferation and Expression of Cyclin E2, Mitogen-Activated Protein Kinases 4 and 7 in Hepatocytes Isolated from a Diethylnitrosamine-Induced Hepatocellular Carcinoma Rat Model.Molecules (Basel, Switzerland) · 2025Article
- CCNE1 Promotes the Progression of Hepatic Precancerous Lesion and the Malignant Phenotype of Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2025Article
- Knockdown of CCNB2 inhibits the tumorigenesis of gastric cancer by regulation of the PI3K/Akt pathway.Scientific reports · 2025Article
- Adaptive survival strategies of rumen microbiota with solid diet deficiency in early life cause epithelial mitochondrial dysfunction.The ISME journal · 2025Article
- Article
- Study of sex-biased differences in genomic profiles in East Asian hepatocellular carcinoma.Discover oncology · 2024Article
- The Role of Z Chromosome Localization GeneInternational journal of molecular sciences · 2024Article
- Quantifying Landscape-Flux via Single-Cell Transcriptomics Uncovers the Underlying Mechanism of Cell Cycle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Predictive three-biomarker panel in peripheral blood mononuclear cells for detecting hepatocellular carcinoma.Scientific reports · 2024Article
- SL-Miner: a web server for mining evidence and prioritization of cancer-specific synthetic lethality.Bioinformatics (Oxford, England) · 2024Article
- Integrating molecular, biochemical, and immunohistochemical features as predictors of hepatocellular carcinoma drug response using machine-learning algorithms.Frontiers in molecular biosciences · 2024Article
- Discovery of Selective Tertiary Amide Inhibitors of Cyclin-Dependent Kinase 2 (CDK2).ACS medicinal chemistry letters · 2023Article
- Expression of Cyclin E1 in hepatic stellate cells is critical for the induction and progression of liver fibrosis and hepatocellular carcinoma in mice.Cell death & disease · 2023Article
- Article
- [Aloin inhibits gastric cancer cell proliferation and migration by suppressing the STAT3/HMGB1 signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
E-type cyclins E1 (CcnE1) and E2 (CcnE2) are regulatory subunits of cyclin-dependent kinase 2 (Cdk2) and thought to control the transition of quiescent cells into the cell cycle. Initial findings indicated that CcnE1 and CcnE2 have largely overlapping functions for cancer development in several tumor entities including hepatocellular carcinoma (HCC). In the present study, we dissected the differential contributions of CcnE1, CcnE2, and Cdk2 for initiation and progression of HCC in mice and patients. To this end, we tested the HCC susceptibility in mice with constitutive deficiency for CcnE1 or CcnE2 as well as in mice lacking Cdk2 in hepatocytes. Genetic inactivation of CcnE1 largely prevented development of liver cancer in mice in two established HCC models, while ablation of CcnE2 had no effect on hepatocarcinogenesis. Importantly, CcnE1-driven HCC initiation was dependent on Cdk2. However, isolated primary hepatoma cells typically acquired independence on CcnE1 and Cdk2 with increasing progression in vitro, which was associated with a gene signature involving secondary induction of CcnE2 and up-regulation of cell cycle and DNA repair pathways. Importantly, a similar expression profile was also found in HCC patients with elevated CcnE2 expression and poor survival. In general, overall survival in HCC patients was synergistically affected by expression of CcnE1 and CcnE2, but not through Cdk2. Our study suggests that HCC initiation specifically depends on CcnE1 and Cdk2, while HCC progression requires expression of any E-cyclin, but no Cdk2.
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