ArticleThe American journal of pathology2004
Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed, 187 citations in OpenAlex.
- A Phase I study of pevonedistat plus capecitabine plus oxaliplatin in patients with advanced gastric cancer refractory to platinum (NCCH-1811).Future science OA · 2021Trial
- Overexpression of CDT1 inhibits cell cycle progression at S phase by interacting with the mini-chromosome maintenance complex and causes DNA damage.FEBS open bio · 2026Article
- Therapeutic efficacy monitoring in canine lymphoma patients via quantifying CDC6 plasma levels.BMC veterinary research · 2026Article
- Phase I study of pevonedistat combined with capecitabine and oxaliplatin in patients with platinum-refractory advanced gastric cancer.Scientific reports · 2025Article
- Putrescine functions as a metabolic checkpoint in replication stress-induced senescence.Cellular and molecular life sciences : CMLS · 2025Article
- Lnc-RAINY regulates genes involved in radiation susceptibility through DNA:DNA:RNA triplex-forming interactions and has tumor therapeutic potential in lung cancers.Non-coding RNA research · 2025Article
- Chromatin Licensing and DNA Replication Factor 1 (CDT1) Is a Potential Prognostic Biomarker Involved in the Malignant Biological Behavior of Glioma.ACS pharmacology & translational science · 2024Article
- Article
- A high-throughput screening identifies MCM chromatin loading inhibitors targeting cells with increased replication origins.iScience · 2024Article
- Comprehensive analysis of aberrantly methylated differentially expressed genes and validation of CDC6 in melanoma.Journal of cancer research and clinical oncology · 2024Article
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.Journal of translational medicine · 2024Article
- Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis.Scientific reports · 2024Article
- CDC6, a key replication licensing factor, is overexpressed and confers poor prognosis in diffuse large B-cell lymphoma.BMC cancer · 2023Article
- A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- High throughput sequencing revealed enhanced cell cycle signaling in SLE patients.Scientific reports · 2023Article
- CDC6: A novel canine tumour biomarker detected in circulating extracellular vesicles.Veterinary and comparative oncology · 2022Article
- Deciphering cervical cancer-associated biomarkers by integrated multi-omics approach.American journal of translational research · 2022Article
- Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma.Frontiers in neuroinformatics · 2022Article
- Small Molecule Inhibitor Targeting CDT1/Geminin Protein Complex Promotes DNA Damage and Cell Death in Cancer Cells.Frontiers in pharmacology · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication licensing ensures once per cell cycle replication and is essential for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1, leads to overreplication and chromosomal instability (CIN) in lower eukaryotes and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung carcinomas, and investigated for putative relations with G(1)/S phase regulators, tumor kinetics, and ploidy. This is the first study of these fundamental licensing elements in primary human lung carcinomas. We herein demonstrate elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of neoplasms, respectively, whereas aberrant expression of hGeminin was observed in 49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048, respectively). Supportive of the observed link between E2F-1 and hCdt1, we provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian cells. Interestingly, hGeminin overexpression was statistically related to increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The significance of these results was underscored by the fact that the latter parameters were independent of p53 within the hCdt1-hCdc6 normally expressing cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6 overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung carcinomas.
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