ArticleOncogene2017
Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed, 62 citations in OpenAlex.
- Review
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Role of sirtuin 1 in depression‑induced coronary heart disease: Molecular pathways and therapeutic potential (Review).Biomedical reports · 2025Review
- Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.Cell death discovery · 2024Article
- Targeting POLD1 to suppress the proliferation and migration of breast cancer MDA-MB-231 cell lines by downregulation of SIRT1.Toxicology research · 2024Article
- SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.Experimental & molecular medicine · 2024Article
- Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.Investigational new drugs · 2024Article
- Review
- C11orf54 promotes DNA repair via blocking CMA-mediated degradation of HIF1A.Communications biology · 2023Article
- SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition.Nature chemical biology · 2023Article
- EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.BMC bioinformatics · 2023Article
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Virtual Screening in the Identification of Sirtuins' Activity Modulators.Molecules (Basel, Switzerland) · 2022Review
- CRIP1 suppresses BBOX1-mediated carnitine metabolism to promote stemness in hepatocellular carcinoma.The EMBO journal · 2022Article
- The Role of HDACs in the Response of Cancer Cells to Cellular Stress and the Potential for Therapeutic Intervention.International journal of molecular sciences · 2022Review
- As a Modulator, Multitasking Roles of SIRT1 in Respiratory Diseases.Immune network · 2022Review
- Sirtuin modulators: past, present, and future perspectives.Future medicinal chemistry · 2022Review
- Targeted Cancer Therapy Based on Acetylation and Deacetylation of Key Proteins Involved in Double-Strand Break Repair.Cancer management and research · 2022Review
- Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response.International journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer treatment remains a challenge for clinical practice and new therapeutic approaches are urgently needed. Loss of functional WEE1 kinase causes DNA replication stress, DNA damage and unscheduled mitotic entry due to elevated CDK activity. The selective WEE1 inhibitor MK-1775 synergize with DNA-damaging agent to inhibit cancer cell growth. Here we report that inhibition of Sirt1 deacetylase through small interfering RNA or selective inhibitor Ex527 greatly enhances MK-1775-induced growth inhibition and apoptosis in human lung cancer cells. We further demonstrate that Sirt1 interacts and deacetylates homologous recombination (HR) repair machinery proteins, including NBS1 and Rad51. Inhibition of Sirt1 impairs HR repair activity, which causes unrepairable damage when combining MK-1775 and Ex527. Meanwhile, combination of MK-1775 and Ex527 induces cooperative antitumor activity in lung cancer xenograft model in vivo. Thus, our study provides a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers.
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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.