ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
HDM2 regulation by AURKA promotes cell survival in gastric cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 65 citations in OpenAlex.
- Combination of AURKA inhibitor and MEK inhibitor strongly enhances G1 arrest and induces synergistic antitumor effect onBiochemistry and biophysics reports · 2025Article
- NKX6.3 modulation of mitotic dynamics and genomic stability in gastric carcinogenesis.Cell communication and signaling : CCS · 2025Article
- SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.Cancer letters · 2024Article
- AURKA inhibition induces Ewing's sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis.Cell death & disease · 2024Article
- Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases.Current medicinal chemistry · 2024Review
- Digging out the biology properties of tRNA-derived small RNA from black hole.Frontiers in genetics · 2023Review
- Chebulagic acid suppresses gastric cancer by inhibiting the AURKA/β-catenin/Wnt pathway.Frontiers in pharmacology · 2023Article
- An in-silico approach leads to explore six genes as a molecular signatures of lung adenocarcinoma.American journal of cancer research · 2023Article
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- circ_0061265 competitively binds to microRNA-885-3p to promote the development of gastric cancer by upregulating AURKA expression.Cancer cell international · 2022Article
- A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer.Cell death & disease · 2022Article
- Unfolded Protein Response Is Activated by Aurora Kinase A in Esophageal Adenocarcinoma.Cancers · 2022Article
- Screening a novel six critical gene-based system of diagnostic and prognostic biomarkers in prostate adenocarcinoma patients with different clinical variables.American journal of translational research · 2022Article
- Integrated pan-cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance.Cancer medicine · 2021Article
- Potential Molecular Targets in the Setting of Chemoradiation for Esophageal Malignancies.Journal of the National Cancer Institute · 2021Review
- Isoforms of the p53 Family and Gastric Cancer: A Ménage à Trois for an Unfinished Affair.Cancers · 2021Review
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- Identification of the hub genes and prognostic indicators of gastric cancer and correlation of indicators with tumor-infiltrating immune cell levels.Journal of Cancer · 2021Article
- WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer.Theranostics · 2021Article
- Influence of gene expression on survival of clear cell renal cell carcinoma.Cancer medicine · 2020Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeSuppression of P53 (tumor protein 53) transcriptional function mediates poor therapeutic response in patients with cancer. Aurora kinase A (AURKA) and human double minute 2 (HDM2) are negative regulators of P53. Herein, we examined the role of AURKA in regulating HDM2 and its subsequent effects on P53 apoptotic function in gastric cancer. EXPERIMENTAL
designPrimary tumors and in vitro gastric cancer cell models with overexpression or knockdown of AURKA were used. The role of AURKA in regulating HDM2 and cell survival coupled with P53 expression and activity were investigated.
resultsOverexpression of AURKA enhanced the HDM2 protein level; conversely, knockdown of endogenous AURKA decreased expression of HDM2 in AGS and SNU-1 cells. Dual co-immunoprecipitation assay data indicated that AURKA was associated with HDM2 in a protein complex. The in vitro kinase assay using recombinant AURKA and HDM2 proteins followed by co-immunoprecipitation revealed that AURKA directly interacts and phosphorylates HDM2 protein in vitro. The activation of HDM2 by AURKA led to induction of P53 ubiquitination and attenuation of cisplatin-induced activation of P53 in gastric cancer cells. Inhibition of AURKA using an investigational small-molecule specific inhibitor, alisertib, decreased the HDM2 protein level and induced P53 transcriptional activity. These effects markedly decreased cell survival in vitro and xenograft tumor growth in vivo. Notably, analysis of immunohistochemistry on tissue microarrays revealed significant overexpression of AURKA and HDM2 in human gastric cancer samples (P < 0.05).
conclusionCollectively, our novel findings indicate that AURKA promotes tumor growth and cell survival through regulation of HDM2-induced ubiquitination and inhibition of P53. Clin Cancer Res; 20(1); 76-86. ©2013 AACR.
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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.