ArticleMolecular cancer research : MCR2013
Diminished origin-licensing capacity specifically sensitizes tumor cells to replication stress.
Article in Molecular cancer research : MCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TopBP1 utilises a bipartite GINS binding mode to support genome replication.Nature communications · 2024Article
- APC/C prevents non-canonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.bioRxiv : the preprint server for biology · 2023Article
- Review
- Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers.Nature communications · 2023Article
- Article
- Decoding the pathogenesis of Diamond-Blackfan anemia using single-cell RNA-seq.Cell discovery · 2022Article
- CDC7 kinase (DDK) inhibition disrupts DNA replication leading to mitotic catastrophe in Ewing sarcoma.Cell death discovery · 2022Article
- Small Molecule Inhibitor Targeting CDT1/Geminin Protein Complex Promotes DNA Damage and Cell Death in Cancer Cells.Frontiers in pharmacology · 2022Article
- DNA Replication Licensing Factors: Novel Targets for Cancer Therapy via Inhibiting the Stemness of Cancer Cells.International journal of biological sciences · 2022Review
- Aberrant MCM10 SUMOylation induces genomic instability mediated by a genetic variant associated with survival of esophageal squamous cell carcinoma.Clinical and translational medicine · 2021Article
- Exploiting Replication Stress as a Novel Therapeutic Intervention.Molecular cancer research : MCR · 2021Review
- Review
- Common fragile sites: protection and repair.Cell & bioscience · 2020Review
- Preparation for DNA replication: the key to a successful S phase.FEBS letters · 2019Review
- Mitotic DNA Synthesis Is Differentially Regulated between Cancer and Noncancerous Cells.Molecular cancer research : MCR · 2019Article
- GINS2 promotes cell proliferation and inhibits cell apoptosis in thyroid cancer by regulating CITED2 and LOXL2.Cancer gene therapy · 2019Article
- The Protective Role of Dormant Origins in Response to Replicative Stress.International journal of molecular sciences · 2018Review
- Article
- Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place.Cancer discovery · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies have shown that dormant licensed replication origins can be exploited to enhance recovery from replication stress. Since tumor cells express high levels of origin-licensing proteins, we examined whether depletion of such factors might specifically sensitize tumor versus nontumor cells. Consistent with previous findings, we observed that three tumor-derived cell lines overexpress ORC1, a licensing component, compared with four nontumor cell lines and that a greater level of ORC1 was required to maintain viability in the tumor cells. We determined siRNA-mediated knockdown conditions for each line that maximally reduced ORC1 but did not impact upon viability, which we considered would optimally deplete dormant origins. ORC1 depletion hypersensitized the tumor-derived cells to hydroxyurea and H202 but did not affect the sensitivity of the nontumor lines. Similar results were observed following depletion of ORC6 or CDC6. Furthermore, codepletion of p53 and ORC1 modestly impaired viability of 1BR3hTERT nontumor fibroblasts and more dramatically caused hypersensitivity to hydroxyurea. Finally, overexpression of the c-Myc oncogene combined with ORC1 depletion in nontumor BJhTERT cells diminished viability. Collectively, these findings suggest that tumor cells may have a reliance on origin-licensing capacity, suggesting that licensing factors could represent a target for drug-based cancer 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.