ArticleCell death & disease2016
CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Targeting the ANGPTL4/NRP1/ABL1/RAD51 axis reverses cisplatin resistance by impairing DNA damage repair in head and neck cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Overexpression of the NEK8 kinase inhibits homologous recombination.DNA repair · 2025Article
- Krüppel-like Factor 4-Deficient Cells Are Sensitive to Etoposide-Induced DNA Damage.Current issues in molecular biology · 2025Article
- Enhanced pharmacological activities of AKR1C3-activated prodrug AST-3424 in cancer cells with defective DNA repair.International journal of cancer · 2025Article
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51.Nucleic acids research · 2024Article
- uPAR (PLAUR) Marks Two Intra-Tumoral Subtypes of Glioblastoma: Insights from Single-Cell RNA Sequencing.International journal of molecular sciences · 2024Article
- Olaparib-ResistantCells · 2023Article
- The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.Journal of hematology & oncology · 2022Review
- Construction and Verification of a Combined Hypoxia and Immune Index for Clear Cell Renal Cell Carcinoma.Frontiers in genetics · 2022Article
- Budding yeast Rad51: a paradigm for how phosphorylation and intrinsic structural disorder regulate homologous recombination and protein homeostasis.Current genetics · 2021Review
- Prognostic significance of uPA and uPAR expression in patients with cervical cancer undergoing radiotherapy.Oncology letters · 2021Article
- Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes.Scientific reports · 2021Article
- Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.Frontiers in endocrinology · 2021Review
- Necrosis-Released HMGB1 (High Mobility Group Box 1) in the Progressive Pulmonary Arterial Hypertension Associated With Male Sex.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Article
- A pan-cancer transcriptome analysis identifies replication fork and innate immunity genes as modifiers of response to the CHK1 inhibitor prexasertib.Oncotarget · 2020Article
- The clinical significance of CHEK1 in breast cancer: a high-throughput data analysis and immunohistochemical study.International journal of clinical and experimental pathology · 2019Article
- Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling.International journal of oncology · 2018Article
- oxLDL inhibits differentiation and functional activity of osteoclasts via scavenger receptor-A mediated autophagy and cathepsin K secretion.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms of DNA damage and repair signaling are not completely understood that hinder the efficiency of cancer therapy. Urokinase-type plasminogen activator receptor (PLAUR) is highly expressed in most solid cancers and serves as a marker of poor prognosis. We show that PLAUR actively promotes DNA repair in cancer cells. On the contrary, downregulation of PLAUR expression results in delayed DNA repair. We found PLAUR to be essential for activation of Checkpoint kinase 1 (CHK1); maintenance of cell cycle arrest after DNA damage in a TP53-dependent manner; expression, nuclear import and recruitment to DNA-damage foci of RAD51 recombinase, the principal protein involved in the homologous recombination repair pathway. Underlying mechanism implies auto-/paracrine signaling of PLAUR/TLR4 receptor complex leading to activation of CHK1 and DNA repair. The signaling is induced by a danger molecule released by DNA-damaged cells and mediates, at least partially, activation of DNA-damage response. This study describes a new mechanism of DNA repair activation initiated by auto-/paracrine signaling of membrane receptors PLAUR/TLR4. It adds to the understanding of role of PLAUR in cancer and provides a rationale for therapeutic targeting of PLAUR/TLR4 interaction in TP53-positive cancers.
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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.