ArticleJournal of cellular physiology2019
The cancer-related transcription factor RUNX2 modulates expression and secretion of the matricellular protein osteopontin in osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis.
Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Clinical significance of secreted phosphoprotein-1 overexpression in cancers.International journal of clinical oncology · 2026Article
- Precision nanomedicine for lung metastatic osteosarcoma: challenges, therapeutic strategies, and perspectives.Materials today. Bio · 2026Review
- Review
- Tumor microenvironment in osteosarcoma: From cellular mechanism to clinical therapy.Genes & diseases · 2025Review
- Dual Regulation and Clinical Application of miR-34 in Virus-Related Tumors Through Anti-Viral Immunity and Tumor Suppression.Drug design, development and therapy · 2025Review
- Review
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair.Biomedicines · 2024Article
- Review
- Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis.International journal of molecular sciences · 2023Review
- Cell-cycle dependent nuclear gene delivery enhances the effects of E-cadherin against tumor invasion and metastasis.Signal transduction and targeted therapy · 2023Article
- Role of RUNX2 in breast cancer development and drug resistance (Review).Oncology letters · 2023Review
- CTR9 drives osteochondral lineage differentiation of human mesenchymal stem cells via epigenetic regulation of BMP-2 signaling.Science advances · 2022Article
- Hydroxygenkwanin suppresses proliferation, invasion and migration of osteosarcoma cells via the miR‑320a/SOX9 axis.Molecular medicine reports · 2022Article
- Pan-cancer Landscape of the RUNX Protein Family Reveals their Potential as Carcinogenic Biomarkers and the Mechanisms Underlying their Action.Journal of translational internal medicine · 2022Article
- Prognostic value and immune characteristics of RUNX gene family in human cancers: a pan-cancer analysis.Aging · 2022Article
- TXNIP inhibits the progression of osteosarcoma through DDIT4-mediated mTORC1 suppression.American journal of cancer research · 2022Article
- Endocrine regulation and metabolic mechanisms of osteopontin in the development and progression of osteosarcoma, metastasis and prognosis.Frontiers in endocrinology · 2022Review
- The cancer-related transcription factor Runx2 combined with osteopontin: a novel prognostic biomarker in resected osteosarcoma.International journal of clinical oncology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR-34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next-generation RNA-sequencing, protein-based assays, as well as the loss- and gain-of-function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell-cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung.
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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 Socratic graph.