ArticleCancer research2013
NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of metastatic solid tumors.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ALDH+ Anaplastic Thyroid Cancer Cells Show Vulnerability to a Pharmacologic Inducer of Centrosome Declustering.Cancer research communications · 2026Article
- Proteomic and phenotypic profiling of replicative-senescent human foreskin fibroblasts under brief heat shock.Cell stress & chaperones · 2026Article
- Covalent Reprogramming of Kinase Binders to Modulate Protein Homeostasis.bioRxiv : the preprint server for biology · 2025Article
- Macrophages downregulate NEDD9 to counteract S. Typhimurium- mediated FAK-AKT activation and lysosome inhibition.Cell death & disease · 2025Article
- Research on biliary atresia and epigenetic factors from the perspective of transcriptomics: identification of key genes and experimental validation.Frontiers in pediatrics · 2025Article
- Enhancer reprogramming underlies therapeutic utility of a SMARCA2 degrader in SMARCA4 mutant cancer.Cell chemical biology · 2024Article
- The significant others of aurora kinase a in cancer: combination is the key.Biomarker research · 2024Review
- CBF-Beta Mitigates PI3K-Alpha-Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer.Molecular cancer research : MCR · 2023Article
- Isorhapontigenin (ISO) inhibits malignant cell transformation, migration, and invasion through MEG3/NEDD9 signaling in Cr(VI)-transformed cells.Toxicology and applied pharmacology · 2023Article
- USP21 contributes to the aggressiveness of laryngeal cancer cells by deubiquitinating and stabilizing AURKA.The Kaohsiung journal of medical sciences · 2023Article
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- Review
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- Moonlighting of mitotic regulators in cilium disassembly.Cellular and molecular life sciences : CMLS · 2021Review
- Aurora kinase A, a synthetic lethal target for precision cancer medicine.Experimental & molecular medicine · 2021Review
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
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- NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice.Oncogene · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Aurora A kinase (AURKA) is overexpressed in 96% of human cancers and is considered an independent marker of poor prognosis. While the majority of tumors have elevated levels of AURKA protein, few have AURKA gene amplification, implying that posttranscriptional mechanisms regulating AURKA protein levels are significant. Here, we show that NEDD9, a known activator of AURKA, is directly involved in AURKA stability. Analysis of a comprehensive breast cancer tissue microarray revealed a tight correlation between the expression of both proteins, significantly corresponding with increased prognostic value. A decrease in AURKA, concomitant with increased ubiquitination and proteasome-dependent degradation, occurs due to depletion or knockout of NEDD9. Reexpression of wild-type NEDD9 was sufficient to rescue the observed phenomenon. Binding of NEDD9 to AURKA is critical for AURKA stabilization, as mutation of S296E was sufficient to disrupt binding and led to reduced AURKA protein levels. NEDD9 confers AURKA stability by limiting the binding of the cdh1-substrate recognition subunit of APC/C ubiquitin ligase to AURKA. Depletion of NEDD9 in tumor cells increases sensitivity to AURKA inhibitors. Combination therapy with NEDD9 short hairpin RNAs and AURKA inhibitors impairs tumor growth and distant metastasis in mice harboring xenografts of breast tumors. Collectively, our findings provide rationale for the use of AURKA inhibitors in treatment of metastatic tumors and predict the sensitivity of the patients to AURKA inhibitors based on NEDD9 expression.
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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.