ArticleOncogenesis2017
Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 95 citations in OpenAlex.
- Article
- AURKA regulates LGR5 in response to Helicobacter Pylori infection by modulating its deubiquitination.Cell death and differentiation · 2026Article
- Survivin/BIRC5-derived peptide disrupts survivin dimerization and cell division and induces multifaceted anti-cancer effects.Molecular therapy. Oncology · 2026Article
- Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.Oncology research · 2026Article
- MicroRNAs as the critical regulators of ubiquitin-proteasome system through F-box protein targeting during tumor progression.Cancer cell international · 2025Review
- FBXO44 Regulates FOXP1 Degradation Through AURKA-Dependent Phosphorylation to Promote Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- FBXL18 increases cell proliferation and reduces cell radiosensitivity in esophageal squamous cell carcinoma.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025Article
- Aberrant DNA methylation as a key modulator of cell death pathways: insights into cancer progression and other diseases.Functional & integrative genomics · 2025Review
- Interplay of aurora kinase a functional residues and Epstein-barr Nuclear Antigen 1 in Epstein-barr virus associated Gastric cancer using AGS cells.BMC cancer · 2025Article
- Cellular Senescence in Hepatocellular Carcinoma: Immune Microenvironment Insights via Machine Learning and In Vitro Experiments.International journal of molecular sciences · 2025Article
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.Cancer letters · 2024Article
- Article
- Gastric Cancer in the Era of Epigenetics.International journal of molecular sciences · 2024Review
- AURKA inhibition induces Ewing's sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis.Cell death & disease · 2024Article
- Caspase-mediated AURKA cleavage at AspTheranostics · 2024Article
- F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.International journal of medical sciences · 2024Review
- Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of Survivin.Journal of Cancer · 2024Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin. Conversely, we demonstrated that AURKA depletion caused a decrease in Survivin protein levels by increasing its ubiquitylation and degradation. Mass spectrometric analysis revealed that upon AURKA depletion, Survivin bound to the FBXL7 E3 ubiquitin ligase, which induced ubiquitin-proteasome degradation of Survivin. In addition, we showed that AURKA regulated FBXL7 both at the levels of transcription and translation. Moreover, proteomic analysis of nuclear AURKA-interacting proteins identified Forkhead box protein P1 (FOXP1). We next showed that AURKA was required for FBXL7 transcription and that AURKA negatively regulated FOXP1-mediated FBXL7 expression. The physiological relevance of the regulation of Survivin by AURKA through the FOXP1-FBXL7 axis was further underscored by the significant positive correlations between AURKA and Survivin expression in gastric cancer patient samples. Moreover, the AURKA depletion or kinase inhibition-induced apoptotic cell death could be reversed by Survivin ectopic overexpression, further supporting that AURKA regulated Survivin to enhance drug resistance. In agreement, inhibition of AURKA synergistically enhanced the cytotoxic effect of DNA-damaging agents in cancer cells by suppressing Survivin expression. Taken together, our data suggest that AURKA restricts Survivin ubiquitylation and degradation in gastric cancer to promote drug resistance and hence the AURKA-Survivin axis can be targeted to promote the efficacy of DNA-damaging agents in gastric cancer.
Identifiers
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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.