ArticleOncogene2021
Nuclear Aurora-A kinase-induced hypoxia signaling drives early dissemination and metastasis in breast cancer: implications for detection of metastatic tumors.
Article in Oncogene, 2021. 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, 24 citations in OpenAlex.
- NN-01-195, a Novel Conjugate of HSP90 and AURKA Inhibitors, Effectively Targets Solid Tumors.Molecular cancer therapeutics · 2026Article
- The ATC12 small molecule inhibits the Aurora-A/TPX2 interaction and impairs the proliferation of breast cancer cells.Cell death & disease · 2026Article
- The AURKA-Selective Inhibitor Alisertib Attenuates Doxorubicin-Induced Hepatotoxicity in Mice via Modulation of IL-17A/NF-κB and STAT3 Signaling Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Exploring Prognostic Gene Factors in Breast Cancer via Machine Learning.Biochemical genetics · 2024Article
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- Mediator kinase inhibitors suppress triple-negative breast cancer growth and extend tumor suppression by mTOR and AKT inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ROS production by mitochondria: function or dysfunction?Oncogene · 2024Review
- Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model.Scientific reports · 2023Article
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation.Life science alliance · 2023Article
- Article
- A new prognostic model including immune biomarkers, genomic proliferation tumor markers (Frontiers in oncology · 2023Article
- Regulating the regulator: a survey of mechanisms from transcription to translation controlling expression of mammalian cell cycle kinase Aurora A.Open biology · 2022Review
- Tamoxifen resistance-related ceRNA network for breast cancer.Frontiers in cell and developmental biology · 2022Article
- Identification of brain endothelial cell-specific genes and pathways in ischemic stroke by integrated bioinformatical analysis.Brain circulationArticle
- Aurora Kinases as Therapeutic Targets in Head and Neck Cancer.Cancer journal (Sudbury, Mass.)Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Metastatic breast cancer causes most breast cancer-associated deaths, especially in triple negative breast cancers (TNBC). The metastatic drivers of TNBCs are still poorly understood, and effective treatment non-existent. Here we reveal that the presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia-Inducible Factor-1) signaling. Nuclear AURKA activates transcription of "hypoxia-induced genes" under normoxic conditions (pseudohypoxia) and without upregulation of oxygen-sensitive HIF1A subunit. We uncover that AURKA preferentially binds to HIF1B and co-localizes with the HIF complex on DNA. The mass-spectrometry analysis of the AURKA complex further confirmed the presence of CBP and p300 along with other TFIIB/RNApol II components. Importantly, the expression of multiple HIF-dependent genes induced by nuclear AURKA (N-AURKA), including migration/invasion, survival/death, and stemness, promote early cancer dissemination. These results indicate that nuclear, but not cytoplasmic, AURKA is a novel driver of early metastasis. Analysis of clinical tumor specimens revealed a correlation between N-AURKA presence and decreased patient survival. Our results establish a mechanistic link between two critical pathways in cancer metastasis, identifying nuclear AURKA as a crucial upstream regulator of the HIF1 transcription complex and a target for anti-metastatic therapy.
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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.