{"doi":"10.1158/0008-5472.c.6497244","title":"Data from Polo-like Kinase 3 Functions as a Tumor Suppressor and Is a Negative Regulator of Hypoxia-Inducible Factor-1α under Hypoxic Conditions","abstract":"<div>Abstract<p>Polo-like kinase 3 (Plk3) is an important mediator of the cellular responses to genotoxic stresses. In this study, we examined the physiologic function of Plk3 by generating <i>Plk3</i>-deficient mice. <i>Plk3<sup>−/−</sup></i> mice displayed an increase in weight and developed tumors in various organs at advanced age. Many tumors in <i>Plk3<sup>−/−</sup></i> mice were large in size, exhibiting enhanced angiogenesis. <i>Plk3<sup>−/−</sup></i> mouse embryonic fibroblasts were hypersensitive to the induction of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions or by nickel and cobalt ion treatments. Ectopic expression of the Plk3-kinase domain (Plk3-KD), but not its Polo-box domain or a Plk3-KD mutant, suppressed the nuclear accumulation of HIF-1α induced by nickel or cobalt ions. Moreover, hypoxia-induced HIF-1α expression was tightly associated with a significant down-regulation of Plk3 expression in HeLa cells. Given the importance of HIF-1α in mediating the activation of the “survival machinery” in cancer cells, these studies strongly suggest that enhanced tumorigenesis in <i>Plk3</i>-null mice is at least partially mediated by a deregulated HIF-1 pathway. [Cancer Res 2008;68(11):4077–85]</p></div>","journal":null,"year":2023,"id":404878,"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":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1183629,"name":"Jingxiang Bai","orcid":null,"position":1,"is_corresponding":false},{"id":259305,"name":"Rulong Shen","orcid":"0000-0001-8143-2582","position":2,"is_corresponding":false},{"id":1183630,"name":"Sharron A.N. Brown","orcid":null,"position":3,"is_corresponding":false},{"id":1183631,"name":"Elena Komissarova","orcid":null,"position":4,"is_corresponding":false},{"id":525116,"name":"Ying Huang","orcid":"0000-0002-8431-6541","position":5,"is_corresponding":false},{"id":544171,"name":"Ning Jiang","orcid":"0000-0002-7152-3621","position":6,"is_corresponding":false},{"id":1183632,"name":"Gregory F. Alberts","orcid":null,"position":7,"is_corresponding":false},{"id":300906,"name":"Max Costa","orcid":"0000-0003-0000-3028","position":8,"is_corresponding":false},{"id":1183257,"name":"Luo Lu","orcid":"0000-0002-1825-4602","position":9,"is_corresponding":false},{"id":302591,"name":"Jeffrey A. Winkles","orcid":"0000-0002-3305-1424","position":10,"is_corresponding":false},{"id":91075,"name":"Wei Dai","orcid":"0000-0002-5558-0685","position":11,"is_corresponding":false},{"id":1183256,"name":"Yali Yang","orcid":"0000-0002-5828-9527","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:49.237119Z","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":[]}