ArticleMolecular and cellular biology2005
The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
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Who cites it
163 citing papers in PubMed, 312 citations in OpenAlex.
- Identification of function for CD44 intracytoplasmic domain (CD44-ICD): modulation of matrix metalloproteinase 9 (MMP-9) transcription via novel promoter response element.The Journal of biological chemistry · 2012Trial
- RUNX2 promotes osteoclast differentiation and bone resorption via the newly identified LncRNA-ROD: implications for alveolar remodeling.International journal of oral science · 2026Article
- KIFC1 engages RUNX2/TGF-β signaling to promote lung cancer bone metastasis via disrupting bone homeostasis.Oncogene · 2026Article
- The Lymphatic-Bone Axis in Cancer Metastasis.Cancers · 2026Review
- Comprehensive multi-omics analysis reveals RUNX1's prognostic value, immune associations, and MUC13-Mediated mechanistic role in hepatocellular carcinoma pathogenesis.Biochemistry and biophysics reports · 2026Article
- AMPK/mTORC2/AKT-473/RUNX2 signaling axis modulates epithelial-mesenchymal transition and bone tropism in breast cancer.Frontiers in oncology · 2026Article
- RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness.Journal of experimental & clinical cancer research : CR · 2025Article
- Bone-protective effects of deer-hide gelatin in cyclophosphamide-induced osteoporosis rats.Frontiers in pharmacology · 2025Article
- Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.Cell death & disease · 2024Article
- ALKBH5-mediated mCell & bioscience · 2024Article
- Exploring the crosstalk of immune cells: The impact of dysregulated RUNX family genes in kidney renal clear cell carcinoma.Heliyon · 2024Article
- Article
- Mesenchymal stem cell-derived exosomes enriched with miR-218 reduce the epithelial-mesenchymal transition and angiogenesis in triple-negative breast cancer cells.European journal of medical research · 2023Article
- Review
- Withaferin A inhibits breast cancer-induced osteoclast differentiation.Molecular carcinogenesis · 2023Article
- Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway.Marine drugs · 2023Article
- Review
- Systemic and local inflammatory response after implantation of biomaterial in critical bone injuries.Acta cirurgica brasileira · 2023Article
- miR-23b-3p, miR-124-3p and miR-218-5p Synergistic or Additive Effects on Cellular Processes That Modulate Cervical Cancer Progression? A Molecular Balance That Needs Attention.International journal of molecular sciences · 2022Review
- Review
103 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The Runx2 (Cbfa1/AML3) transcription factor and matrix metalloproteinase 9 (MMP9) are key regulators of growth plate maturation and bone formation. The genes for both proteins are characteristic markers of breast and prostate cancer cells that metastasize to bone. Here we experimentally addressed the compelling question of whether Runx2 and MMP are functionally linked. By cDNA expression array analysis, we identified MMP9 as a novel downstream target of Runx2. Like that of MMP13, MMP9 expression is nearly depleted in Runx2 mutant mice. Chromatin immunoprecipitation and electrophoretic mobility shift assays revealed the recruitment of Runx2 to the MMP9 promoter. We show by mutational analysis that the Runx2 site mediates transactivation of the MMP9 promoter in osteoblasts (MC3T3-E1) and nonosseous (HeLa) cells. The overexpression of Runx2 by adenovirus delivery in nonmetastatic (MCF-7) and metastatic breast (MDA-MB-231) and prostate (PC3) cancer cell lines significantly increases the endogenous levels of MMP9. The knockdown of Runx2 by RNA interference decreases MMP9 expression, as well as that of other Runx2 target genes, including the genes for MMP13 and vascular endothelial growth factor. Importantly, we have demonstrated using a cell invasion assay that Runx2-regulated MMP9 levels are functionally related to the invasion properties of cancer cells. These results are consistent with Runx2 control of multiple genes that contribute to the metastatic properties of cancer cells and their activity in the bone microenvironment.
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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.