ArticleScientific reports2019
Cell adhesion to collagen promotes leukemia resistance to doxorubicin by reducing DNA damage through the inhibition of Rac1 activation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 27 citations in OpenAlex.
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Increased efficacy of PARP inhibitors against cisplatin-sensitive and -resistant ovarian cancer cells mediated via ATR and ATM inhibition.Cell death discovery · 2025Article
- Targeting Integrin α2 to Overcome Imatinib Resistance in Chronic Myeloid Leukemia Cells.Biomolecules · 2025Article
- Loss of Predicted Cell Adhesion Molecule MPZL3 Promotes EMT in Ovarian Cancer.Cancer research communications · 2025Article
- Review
- Constitutive activation of the Src-family kinases Fgr and Hck enhances the tumor burden of acute myeloid leukemia cells in immunocompromised mice.Scientific reports · 2025Article
- Exosomal miR-92b-5p regulates N4BP1 to enhance PTEN mono-ubiquitination in doxorubicin-resistant AML.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes.Cancers · 2024Article
- Advancements in the impact of human microbiota and probiotics on leukemia.Frontiers in microbiology · 2024Review
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells.Precision clinical medicine · 2022Article
- Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.Antibiotics (Basel, Switzerland) · 2021Review
- Adhesion Molecules Involved in Stem Cell Niche Retention During Normal Haematopoiesis and in Acute Myeloid Leukaemia.Frontiers in immunology · 2021Review
- Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components.Frontiers in genetics · 2021Review
- CAM-DR: Mechanisms, Roles and Clinical Application in Tumors.Frontiers in cell and developmental biology · 2021Review
- Article
- Rac1 repression reverses chemoresistance by targeting tumor metabolism.Cancer biology & therapy · 2020Article
- Cadherins, Selectins, and Integrins in CAM-DR in Leukemia.Frontiers in oncology · 2020Review
- Reciprocal Interplay Between Fibrillar Collagens and Collagen-Binding Integrins: Implications in Cancer Progression and Metastasis.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chemoresistance is a major hurdle in anti-cancer therapy. Growing evidence indicates that integrin-mediated cell adhesion to extracellular matrix plays a major role in chemoresistance. However, the underlying mechanisms are not fully understood. We have previously shown that the collagen-binding integrin α2β1 promoted doxorubicin resistance in acute T cell lymphoblastic leukemia (T-ALL). In this study, we found that acute myeloid leukemia (AML) cell lines also express α2β1 integrin and collagen promoted their chemoresistance as well. Furthermore, we found that high levels of α2 integrin correlate with worse overall survival in AML. Our results showed that doxorubicin-induced apoptosis in leukemic cells is associated with activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) and that collagen inhibited this pathway. The protective effect of collagen is associated with the inhibition of Rac1-induced DNA damage as evaluated by the comet assay and the phosphorylated levels of histone H2AX (γ-H2AX). Together these results show that by inhibiting pro-apoptotic Rac1, α2β1 integrin can be a major pathway protecting leukemic cells from genotoxic agents and may thus represent an important therapeutic target in anti-cancer treatment.
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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.