ArticleCell death & disease2022
Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Multidimensional Regulatory Network and Spatiotemporal Specificity of FOXO Transcription Factors in Digestive System Tumors: Recent Advances.International journal of molecular sciences · 2026Review
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Targeting Skp2 by Tanshinone IIA overcomes chemoresistance in colorectal cancer.Cell biology and toxicology · 2025Article
- E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance.Cell death discovery · 2025Article
- Aurora kinase A expression in pleomorphic adenoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands: an immunohistochemical study.BMC oral health · 2025Article
- The biological function and prognostic significance of ferroptosis-related genes in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- PLEKHA4 upregulation regulates KIRC cell proliferation through β‑catenin signaling.Molecular medicine reports · 2025Article
- Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.Cancer reports (Hoboken, N.J.) · 2024Article
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- LncRNA LBX2-AS1 promotes proliferation and migratory capacity of clear cell renal cell carcinoma through mitophagy.European journal of medical research · 2024Article
- FOXO3a-interacting proteins' involvement in cancer: a review.Molecular biology reports · 2024Review
- Targeting the deubiquitinaseOncology reports · 2023Review
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Article
- SKP2 E3 ligase in urological malignancies: a critical regulator of the cell cycle and therapeutic target.Cell cycle (Georgetown, Tex.)Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is a common malignant tumor in the world. Histologically, most of RCC is classified as clear cell renal cell carcinoma (ccRCC), which is the most prevalent subtype. The overall survival of patients with ccRCC is poor, thus it is urgent to further explore its mechanism and target. S-phase kinase-associated protein 2 (SKP2) is overexpressed in a variety of human cancers and is associated with poor prognosis by enhancing tumor progression. However, it is unclear whether or how SKP2 is involved in ccRCC progression. Here, we reported that overexpression of SKP2 enhanced cell proliferation of ccRCC, while SKP2 depletion exhibited the opposite effect. Bioinformatic analyses found that SKP2 was positively correlated with Aurora-A (Aur-A) in ccRCC. The protein and mRNA levels of SKP2 were elevated or reduced by Aur-A overexpression or silencing, respectively. It was further found that Aur-A caused an increase phosphorylation of FOXO3A, which is a negatively transcription factor for SKP2. Interestingly, SKP2 mediated ubiquitylation and degradation of FOXO3A depend on the kinase activity of Aur-A. The combination of Aur-A inhibitor MLN8237 and SKP2 inhibitor SZL P1-41 showed a synergistic tumor growth inhibition in vivo and in vitro of ccRCC models. Thus, our data reveal that Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in ccRCC, and the double inhibition of SKP2 and Aur-A shows significant synergistic effect, which indicates a potential new therapeutic strategy for ccRCC.
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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.