ArticleOncotarget2015
Statin-induced depletion of geranylgeranyl pyrophosphate inhibits cell proliferation by a novel pathway of Skp2 degradation.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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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.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Atorvastatin: A Focus on Cervical and Head and Neck Cancers.Pharmaceutics · 2025Article
- Effects of statins beyond lipid-lowering agents in ART-treated HIV infection.Frontiers in immunology · 2024Review
- Novel Effects of Statins on Cancer via Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Fungal Secondary Metabolites as Inhibitors of the Ubiquitin-Proteasome System.International journal of molecular sciences · 2021Review
- Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Pleiotropic effects of statins: A focus on cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Statins: Could an old friend help in the fight against COVID-19?British journal of pharmacology · 2020Review
- Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells.Cancers · 2020Article
- Skp2 modulates proliferation, senescence and tumorigenesis of glioma.Cancer cell international · 2020Article
- Pleiotropic use of Statins as non-lipid-lowering drugs.International journal of biological sciences · 2020Review
- Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Paeoniflorin exerts antitumor effects by inactivating S phase kinase-associated protein 2 in glioma cells.Oncology reports · 2018Article
- FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27Haematologica · 2017Article
- Caspases uncouple p27(Kip1) from cell cycle regulated degradation and abolish its ability to stimulate cell migration and invasion.Oncogene · 2016Article
- Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma.Oncotarget · 2016Article
- Mechanisms for autophagy modulation by isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells.Oncotarget · 2015Article
- Effects of Lovastatin on Brain Cancer Cells.Cell transplantationReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Statins, such as lovastatin, can induce a cell cycle arrest in the G1 phase. This robust antiproliferative activity remains intact in many cancer cells that are deficient in cell cycle checkpoints and leads to an increased expression of CDK inhibitor proteins p27Kip1 and p21Cip1. The molecular details of this statin-induced growth arrest remains unclear. Here we present evidence that lovastatin can induce the degradation of Skp2, a subunit of the SCFSkp2 ubiquitin ligase that targets p27Kip1 and p21Cip1 for proteasomal destruction. The statin-induced degradation of Skp2 is cell cycle phase independent and does not require its well characterised degradation pathway mediated by APC/CCdh1- or Skp2 autoubiquitination. An N-terminal domain preceding the F-box of Skp2 is both necessary and sufficient for its statin mediated degradation. The degradation of Skp2 results from statin induced depletion of geranylgeranyl isoprenoid intermediates of cholesterol biosynthesis. Inhibition of geranylgeranyl-transferase-I also promotes APC/CCdh1- independent degradation of Skp2, indicating that de-modification of a geranylgeranylated protein triggers this novel pathway of Skp2 degradation.
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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.