ArticleMolecular cancer research : MCR2012
MYC-driven tumorigenesis is inhibited by WRN syndrome gene deficiency.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- The Zinc Finger Ran-Binding Protein 3 (ZRANB3): An Advanced Perspective.International journal of molecular sciences · 2026Review
- Specific Monitoring the DNA Helicase Function via Anchor-Embedded DNA Probe.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploiting replication stress for synthetic lethality in MYC-driven cancers.American journal of cancer research · 2025Review
- Review
- Review
- MYC and therapy resistance in cancer: risks and opportunities.Molecular oncology · 2022Review
- Synthetic Lethal Interactions of RECQ Helicases.Trends in cancer · 2021Review
- The UVSSA complex alleviates MYC-driven transcription stress.The Journal of cell biology · 2021Article
- Methods to Study Myc-Regulated Cellular Senescence: An Update.Methods in molecular biology (Clifton, N.J.) · 2021Article
- WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells.BMC molecular and cell biology · 2020Article
- Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress.International journal of molecular sciences · 2018Review
- MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.Cell death & disease · 2018Article
- Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas.Cell systems · 2018Article
- WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells.Journal of hematology & oncology · 2016Article
- The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress.Cell death and differentiation · 2016Article
- Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer.International journal of molecular sciences · 2015Article
- MYC is a critical target of FBXW7.Oncotarget · 2015Article
- Identification and pharmacological inactivation of the MYCN gene network as a therapeutic strategy for neuroblastic tumor cells.The Journal of biological chemistry · 2015Article
- Multi-Scale Genomic, Transcriptomic and Proteomic Analysis of Colorectal Cancer Cell Lines to Identify Novel Biomarkers.PloS one · 2015Article
- MYC and the control of DNA replication.Cold Spring Harbor perspectives in medicine · 2014Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
MYC-induced DNA damage is exacerbated in WRN-deficient cells, leading to replication stress and accelerated cellular senescence. To determine whether WRN deficiency impairs MYC-driven tumor development, we used both xenograft and autochthonous tumor models. Conditional silencing of WRN expression in c-MYC overexpressing non-small cell lung cancer xenografts impaired both tumor establishment and tumor growth. This inhibitory effect of WRN knockdown was accompanied by increased DNA damage, decreased proliferation, and tumor necrosis. In the Eμ-Myc mouse model of B-cell lymphoma, a germline mutation in the helicase domain of Wrn (Wrn(Δhel/Δhel)) resulted in a significant delay in emergence of lethal lymphomas, extending tumor-free survival by more than 30%. Analysis of preneoplastic B cells from Eμ-Myc Wrn mutant mice revealed increased DNA damage, elevation of senescence markers, and decreased proliferation in comparison with cells from age-matched Eμ-Myc mice. Immunohistochemical and global gene expression analysis of overt Eμ-Myc Wrn(Δhel/Δhel) lymphomas showed a marked increase in expression of the CDK inhibitor, p16(Ink4a), as well as elevation of TAp63, a known mediator of senescence. Collectively, these studies show that in the context of Myc-associated tumorigenesis, loss of Wrn amplifies the DNA damage response, both in preneoplastic and neoplastic tissue, engaging activation of tumor suppressor pathways. This leads to inhibition of tumor growth and prolonged tumor-free survival. Targeting WRN or its enzymatic function could prove to be an effective strategy in the treatment of MYC-associated cancers.
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