{"doi":"10.33915/etd.10163","title":"Nuclear Aurora-A kinase-induced hypoxia signaling drives dissemination and metastasis in breast cancer.","abstract":"Metastatic breast cancer causes the vast majority of cancer-associated deaths, especially in triple negative breast cancers (TNBC). TNBC is still poorly understood and has no effective treatment. Here we reveal that presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia induced factor-1) signaling. The nuclear AURKA in the complex with constitutively expressed HIF-1β subunit activates transcription of “hypoxia induced genes” under normoxic conditions (the phenomenon called pseudohypoxia) without upregulation of oxygen-sensitive HIF-1α subunit. We uncover that AURKA preferentially binds to and phosphorylates HIF-1β, and co-localizes with HIF complex on DNA. The mass spectrometry analysis of AURKA complex further confirmed presence of CBP and p300 along with other TFIIB/RNApol II components. Importantly, expression of multiple HIF-dependent genes including migration/invasion, survival/death and stemness induced by nuclear AURKA promote early cancer dissemination. These results indicate that nuclear pool of AURKA, but not cytoplasmic, is a novel driver of early metastatic dissemination. Analysis of clinical tumor specimens revealed a correlation between HIF- 1α and AURKA levels and an association of their co-expression to decreased patient survival. Our results establish a mechanistic linkage between two key pathways in cancer metastasis, identifying nuclear AURKA as a critical upstream regulator of HIF-1 transcription complex, and a target for anti-metastatic therapy.","journal":null,"year":2021,"id":227971,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":709079,"name":"Kristina M Whately","orcid":"0000-0002-5908-8145","position":0,"is_corresponding":true}],"reference_count":137,"raw_metadata":null,"created_at":"2026-07-18T23:54:46.312854Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}