ArticleOncotarget2017
Integrin αVβ3 silencing sensitizes malignant glioma cells to temozolomide by suppression of homologous recombination repair.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- α7 integrin co-regulates chromatin accessibility and gene expression in HPV-negative head and neck cancer.Signal transduction and targeted therapy · 2026Article
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Resistance to radiation enhances metastasis by altering RNA metabolism.Science advances · 2025Article
- Down-Regulation of CEND1 Expression Contributes to The Progression and Temozolomide Resistance of Glioma.Cell journal · 2023Article
- The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.Molecular therapy oncolytics · 2022Review
- The DNA Double-Strand Break Repair in Glioma: Molecular Players and Therapeutic Strategies.Molecular neurobiology · 2022Review
- Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers.Brain sciences · 2022Review
- Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?Pharmaceutics · 2022Review
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Targeting c-IAP1, c-IAP2, and Bcl-2 Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment.Cancers · 2021Article
- Localization matters: nuclear-trapped Survivin sensitizes glioblastoma cells to temozolomide by elevating cellular senescence and impairing homologous recombination.Cellular and molecular life sciences : CMLS · 2021Article
- Targeted Therapy to β3 Integrin Reduces Chemoresistance in Breast Cancer Bone Metastases.Molecular cancer therapeutics · 2021Article
- Article
- Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence.Nucleic acids research · 2020Article
- Combination therapy of cold atmospheric plasma (CAP) with temozolomide in the treatment of U87MG glioblastoma cells.Scientific reports · 2020Article
- 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
- Integrin Crosstalk Contributes to the Complexity of Signalling and Unpredictable Cancer Cell Fates.Cancers · 2020Review
- The predictive capability of immunohistochemistry and DNA sequencing for determiningOncotarget · 2019Article
- ITGB3/CD61: a hub modulator and target in the tumor microenvironment.American journal of translational research · 2019Review
- The Extracellular, Cellular, and Nuclear Stiffness, a Trinity in the Cancer Resistome-A Review.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrins have been suggested as possible targets in anticancer therapy. Here we show that knockdown of integrins αVβ3, αVβ5, α3β1 and α4β1 and pharmacological inhibition using a cyclo-RGD integrin αVβ3/αVβ5 antagonist sensitized multiple high-grade glioma cell lines to temozolomide (TMZ)-induced cytotoxicity. The greatest effect was observed in LN229 cells upon integrin β3 silencing, which led to inhibition of the FAK/Src/Akt/NFκB signaling pathway and increased formation of γH2AX foci. The integrin β3 knockdown led to the proteasomal degradation of Rad51, reduction of Rad51 foci and reduced repair of TMZ-induced DNA double-strand breaks by impairing homologous recombination efficiency. The down-regulation of β3 in Rad51 knockdown (LN229-Rad51kd) cells neither further sensitized them to TMZ nor increased the number of γH2AX foci, confirming causality between β3 silencing and Rad51 reduction. RIP1 was found cleaved and IκBα significantly less degraded in β3-silenced/TMZ-exposed cells, indicating inactivation of NFκB signaling. The anti-apoptotic proteins Bcl-xL, survivin and XIAP were proteasomally degraded and caspase-3/-2 cleaved. Increased H2AX phosphorylation, caspase-3 cleavage, reduced Rad51 and RIP1 expression, as well as sustained IκBα expression were also observed in mouse glioma xenografts treated with the cyclo-RGD inhibitor and TMZ, confirming the molecular mechanism in vivo. Our data indicates that β3 silencing in glioma cells represents a promising strategy to sensitize high-grade gliomas to TMZ 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.