ArticleMolecular and cellular biology2018
β1-Integrin Impacts Rad51 Stability and DNA Double-Strand Break Repair by Homologous Recombination.
Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks.iScience · 2026Article
- UHRF1 Controls the Timing of RAD51 Removal During DNA Damage Repair Through Suppressing RFWD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mapping the transcriptional and epigenetic landscape of organotypic endothelial diversity in the developing and adult mouse.Nature cardiovascular research · 2025Article
- KIN17 functions in DNA damage repair and chemosensitivity by modulating RAD51 in hepatocellular carcinoma.Human cell · 2024Article
- Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis.Cell death & disease · 2024Article
- Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
- Polymerase iota (POLI) confers radioresistance of esophageal squamous cell carcinoma by regulating RAD51 stability and facilitating homologous recombination.Cell death discovery · 2023Article
- GAPDH facilitates homologous recombination repair by stabilizing RAD51 in an HDAC1-dependent manner.EMBO reports · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Article
- Beta human papillomavirus 8 E6 allows colocalization of non-homologous end joining and homologous recombination repair factors.PLoS pathogens · 2022Article
- TRIM44 mediated p62 deubiquitination enhances DNA damage repair by increasing nuclear FLNA and 53BP1 expression.Oncogene · 2021Article
- Budding yeast Rad51: a paradigm for how phosphorylation and intrinsic structural disorder regulate homologous recombination and protein homeostasis.Current genetics · 2021Review
- PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells.Signal transduction and targeted therapy · 2021Article
- Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components.Frontiers in genetics · 2021Review
- Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation.Frontiers in oncology · 2021Article
- The Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51.Frontiers in oncology · 2021Article
- c-Abl Tyrosine Kinase Is Regulated Downstream of the Cytoskeletal Protein Synemin in Head and Neck Squamous Cell Carcinoma Radioresistance and DNA Repair.International journal of molecular sciences · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms underlying resistance to radiotherapy in breast cancer cells remain elusive. Previously, we reported that elevated β1-integrin is associated with enhanced breast cancer cell survival postirradiation, but how β1-integrin conferred radioresistance was unclear. Ionizing radiation (IR) induced cell killing correlates with the efficiency of DNA double-strand break (DSB) repair, and we found that nonmalignant breast epithelial (S1) cells with low β1-integrin expression have a higher frequency of S-phase-specific IR-induced chromosomal aberrations than the derivative malignant breast (T4-2) cells with high β1-integrin expression. In addition, there was an increased frequency of IR-induced homologous recombination (HR) repairosome focus formation in T4-2 cells compared with that of S1 cells. Cellular levels of Rad51 in T4-2 cells, a critical factor in HR-mediated DSB repair, were significantly higher. Blocking or depleting β1-integrin activity in T4-2 cells reduced Rad51 levels, while ectopic expression of β1-integrin in S1 cells correspondingly increased Rad51 levels, suggesting that Rad51 is regulated by β1-integrin. The low level of Rad51 protein in S1 cells was found to be due to rapid degradation by the ubiquitin proteasome pathway (UPP). Furthermore, the E3 ubiquitin ligase RING1 was highly upregulated in S1 cells compared to T4-2 cells. Ectopic β1-integrin expression in S1 cells reduced RING1 levels and increased Rad51 accumulation. In contrast, β1-integrin depletion in T4-2 cells significantly increased RING1 protein levels and potentiated Rad51 ubiquitination. These data suggest for the first time that elevated levels of the extracellular matrix receptor β1-integrin can increase tumor cell radioresistance by decreasing Rad51 degradation through a RING1-mediated proteasomal pathway.
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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.