ArticleCancer research2014
Integrin αvβ6 promotes an osteolytic program in cancer cells by upregulating MMP2.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 68 citations in OpenAlex.
- The role of extracellular vesicles-associated proteins markers in prostate cancer: a review.Discover oncology · 2026Review
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- Orchestrating Tumor Metastasis: Exosomes as Master Regulators of the Local and Distant Microenvironment.International journal of biological sciences · 2026Review
- The integrin α2-osteoclast axis: a key driver of bone destruction and therapeutic target in osteosarcoma.Journal of translational medicine · 2025Article
- Integrins from extracellular vesicles as players in tumor microenvironment and metastasis.Cancer metastasis reviews · 2025Review
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Evaluation of [Molecular imaging and biology · 2025Article
- Synthetic Protein-to-DNA Input Exchange for Protease Activity Detection Using CRISPR-Cas12a.Analytical chemistry · 2024Article
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression.Molecular cancer research : MCR · 2023Article
- Review
- Review
- The role of integrin family in bone metabolism and tumor bone metastasis.Cell death discovery · 2023Review
- Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFInternational journal of molecular sciences · 2023Article
- Small extracellular vesicle-mediatedCancer biology & therapy · 2022Article
- Formation of pre-metastatic bone niche in prostate cancer and regulation of traditional chinese medicine.Frontiers in pharmacology · 2022Review
- Exosomes and organ-specific metastasis.Molecular therapy. Methods & clinical development · 2021Review
- Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis (Review).Molecular medicine reports · 2021Review
- Article
- Targeting IL-3Rα on tumor-derived endothelial cells blunts metastatic spread of triple-negative breast cancer via extracellular vesicle reprogramming.Oncogenesis · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
The molecular circuitries controlling osseous prostate metastasis are known to depend on the activity of multiple pathways, including integrin signaling. Here, we demonstrate that the αvβ6 integrin is upregulated in human prostate cancer bone metastasis. In prostate cancer cells, this integrin is a functionally active receptor for fibronectin and latency-associated peptide-TGF-β1; it mediates attachment and migration upon ligand binding and is localized in focal contacts. Given the propensity of prostate cancer cells to form bone metastatic lesions, we investigated whether the αvβ6 integrin promotes this type of metastasis. We show for the first time that αvβ6 selectively induces matrix metalloproteinase 2 (MMP2) in vitro in multiple prostate cancer cells and promotes osteolysis in vivo in an immunodeficient mouse model of bone metastasis through upregulation of MMP2, but not MMP9. The effect of αvβ6 on MMP2 expression and activity is independent of androgen receptor in the analyzed prostate cancer cells. Increased levels of parathyroid hormone-related protein (PTHrP), known to induce osteoclastogenesis, were also observed in αvβ6-expressing cells. However, by using MMP2 short hairpin RNA, we demonstrate that the αvβ6 effect on bone loss is due to upregulation of soluble MMP2 by the cancer cells, not due to changes in tumor growth rate. Another related αv-containing integrin, αvβ5, fails to show similar responses, underscoring the significance of αvβ6 activity. Overall, these mechanistic studies establish that expression of a single integrin, αvβ6, contributes to the cancer cell-mediated program of osteolysis by inducing matrix degradation through MMP2. Our results open new prospects for molecular therapy for metastatic bone disease.
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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.