ArticleOncogene2021
Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 98 citations in OpenAlex.
- Targeting Integrins in Triple Negative Breast Cancer: Therapeutic Potential of Monoclonal Antibodies, PARP Inhibitors, Synthetic Peptides, and Aptamers.Cancer medicine · 2026Review
- A CTC/DTC-centered temporal framework of bone metastasis: From dissemination to dormancy and reactivation.Journal of bone oncology · 2026Review
- Integrin α5β1 in pancreatic ductal adenocarcinoma: Tumour‒stroma crosstalk, hypoxia and therapeutic targeting.Clinical and translational medicine · 2026Review
- Downregulation of PIEZO1 Activity Promotes Breast Cancer Cell Survival under Shear Stress by Modulating β-Catenin and BCL2.Cancer research communications · 2026Article
- ITGA5 as a Dual Regulator of Epithelial-Mesenchymal Transition and Epithelial Cell Anoikis Resistance: Functional Validation and Drug Prediction.Cell proliferation · 2026Article
- TROP2 promotes bone metastasis of colorectal cancer through interaction with the fibronectin-integrin axis.Cellular and molecular life sciences : CMLS · 2026Article
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- RPRD1A drives lenvatinib resistance in hepatocellular carcinoma via the ITGA5-FAK signaling axis.Molecular biomedicine · 2026Article
- The Osteoblastic Microenvironment Determines the Fate of Breast Cancer Cells Disseminated in the Bone Marrow.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Extracellular matrix polysaccharides and glycoproteins in ovarian cancer: structural-functional macromolecular perspectives and potential exosome-derived biomarkers.Cell communication and signaling : CCS · 2026Review
- Article
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.Cancer letters · 2026Article
- In Situ Biomineralization Enhances Mitochondrial Transplantation to Differentiating Osteoclast Precursors for Suppressing Cancer-Induced Osteolysis.Research (Washington, D.C.) · 2026Article
- Article
- Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116Nature genetics · 2025Article
- The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.Journal of translational medicine · 2025Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Macrophages in the premetastatic and metastatic niche: key functions and therapeutic directions.Journal of translational medicine · 2025Review
- Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets.Cancer medicine · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient's treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.
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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.