ArticleBreast cancer research : BCR2006
The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.
Article in Breast cancer research : BCR, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00555256 (A Phase I Study of SUNITINIB and Rapamycin in Advanced Non-Small Cell Lung Cancer), which is not on this map. Cited by 43 papers.
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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.
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.
A Phase I Study of SUNITINIB and Rapamycin in Advanced Non-Small Cell Lung Cancer (NSCLC)
Who cites it
43 citing papers in PubMed, 88 citations in OpenAlex.
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- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- Therapeutic role of mTOR inhibitors in control of SARS-CoV-2 viral replication.Molecular biology reports · 2023Review
- Oxadiazol-based mTOR inhibitors with potent antiproliferative activities: synthetic and computational modeling.Molecular diversity · 2022Article
- A gene signature consisting of ubiquitin ligases and deubiquitinating enzymes of SKP2 is associated with clinical outcome in breast cancer.Scientific reports · 2022Article
- Prolonged cetuximab treatment promotes p27Scientific reports · 2021Article
- Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer.Cancer cell international · 2021Article
- Everolimus Alleviates Renal Allograft Interstitial Fibrosis by Inhibiting Epithelial-to-Mesenchymal Transition Not OnlyFrontiers in immunology · 2021Article
- Clinicopathological features of pseudomyogenic hemangioendothelioma and precision therapy based on whole exome sequencing.Cancer communications (London, England) · 2020Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.Breast cancer research : BCR · 2018Article
- EDG2 enhanced the progression of hepatocellular carcinoma by LPA/PI3K/AKT/ mTOR signaling.Oncotarget · 2017Article
- Protein-mediated viral latency is a novel mechanism for Merkel cell polyomavirus persistence.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer.Molecular cancer · 2017Article
- A brain proteomic investigation of rapamycin effects in theMolecular autism · 2017Article
- Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) Signaling Pathway.International journal of molecular sciences · 2016Article
- BRCA1 inhibits AR-mediated proliferation of breast cancer cells through the activation of SIRT1.Scientific reports · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionLoss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown.
methodsThe expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1.
resultsRapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1.
conclusionThese results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment.
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