ArticleCancer research2020
Obesity/Type 2 Diabetes-Associated Liver Tumors Are Sensitive to Cyclin D1 Deficiency.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Cyclin D1 regulates the hepatic response to feeding: Evidence for non-cell cycle roles in the liver.bioRxiv : the preprint server for biology · 2026Article
- F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression.Nature communications · 2025Article
- Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.Nature cell biology · 2025Article
- Liver cancer burden attributable to high body mass index and high fasting plasma glucose in BRICS countries (1990-2021): a Global Burden of Disease 2021 analysis with projections to 2050.Frontiers in oncology · 2025Article
- ANTI-INFLAMMATORY AND METABOLIC EFFECTS OFAfrican journal of infectious diseases · 2025Article
- Blocking interleukin-1 receptor type 1 (IL-1R1) signaling in hepatocytes slows down diethylnitrosamine-induced liver tumor growth in obese mice.Hepatology communications · 2024Article
- The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Monitoring the Cell Cycle of Tumor Cells in Mouse Models of Human Cancer.Cold Spring Harbor perspectives in medicine · 2023Article
- [Bioinformatics Analysis of Hub Genes of Diabetic Foot Ulcer and Their Biofunctions].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Article
- Retinal Transcriptome and Cellular Landscape in Relation to the Progression of Diabetic Retinopathy.Investigative ophthalmology & visual science · 2022Article
- Mechanism ofNutrients · 2022Article
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
- The SREBP-dependent regulation of cyclin D1 coordinates cell proliferation and lipid synthesis.Frontiers in oncology · 2022Article
- Functionalized Selenium Nanoparticles Synergizes With Metformin to Treat Breast Cancer Cells Through Regulation of Selenoproteins.Frontiers in bioengineering and biotechnology · 2021Article
- Obesity, Type 2 Diabetes, and Cancer Risk.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer progression. Here we show that cyclin D1 is greatly elevated in human livers with diabetes and is among the most significantly upregulated genes in obese/diabetic liver tumors. Liver-specific cyclin D1 deficiency protected obese/diabetic mice against hepatic tumorigenesis, whereas lean/nondiabetic mice developed tumors irrespective of cyclin D1 status. Cyclin D1 dependency positively correlated with liver cancer sensitivity to palbociclib, an FDA-approved CDK4 inhibitor, which was effective in treating orthotopic liver tumors under obese/diabetic conditions. The antidiabetic drug metformin suppressed insulin-induced hepatic cyclin D1 expression and protected against obese/diabetic hepatocarcinogenesis. These results indicate that the cyclin D1-CDK4 complex represents a potential selective therapeutic vulnerability for liver tumors in obese/diabetic patients. SIGNIFICANCE: Obesity/diabetes-associated liver tumors are specifically vulnerable to cyclin D1 deficiency and CDK4 inhibition, suggesting that the obese/diabetic environment confers cancer-selective dependencies that can be therapeutically exploited.
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Registered trials
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