The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
The Runx2 Osteogenic Transcription Factor Regulates Matrix Metalloproteinase 9 in Bone Metastatic Cancer Cells and Controls Cell Invasion
Open accessAbstract
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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Cites
New functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Yergeau, D. A., Hetherington, C. J., Wang, Q., Zhang, P., Sharpe, A. H., Binder, M., Marín-Padilla, M., Tenen, D. G., Speck, N. A., & Zhang, D.-E. (1997) · Nature Genetics · doi:10.1038/ng0397-303 · Cited by 346
Regulation of Tissue Inhibitor of Metalloproteinase 1 Gene Transcription by RUNX1 and RUNX2
Bertrand-Philippe, M., Ruddell, R. G., Arthur, M. J. P., Thomas, J., Mungalsingh, N., & Mann, D. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311804200 · Cited by 49 · cited 1×
“(7) showed that JunD and Runx factors assemble at the adjacent SRE and UTE-1 sites in the TIMP1 promoter and form functional interactions that stimulate transcription.”
Background
Cited by
Guidelines and definitions for research on epithelial-mesenchymal transition
Yang, J., Antin, P., Berx, G., Blanpain, C., Brabletz, T., Bronner, M., Campbell, K., Cano, A., Casanova, J., Christofori, G., et al. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0237-9 · Cited by 2,226
Targeting transcription factors in cancer — from undruggable to reality
Bushweller, J. H. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0196-7 · Cited by 919
The regulation of matrix metalloproteinases and their inhibitors
Clark, I. M., Swingler, T. E., Sampieri, C. L., & Edwards, D. R. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.12.006 · Cited by 555
Molecular Biology of Bone Metastasis
Kingsley, L. A., Fournier, P. G. J., Chirgwin, J. M., & Guise, T. A. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0234 · Cited by 435
Akech, J., Wixted, J. J., Bedard, K., van der Deen, M., Hussain, S., Guise, T. A., van Wijnen, A. J., Stein, J. L., Languino, L. R., Altieri, D. C., et al. (2010) · Oncogene · doi:10.1038/onc.2009.389 · Cited by 295
Self-citation
Metadata
- Authors
- Pratap, J., Javed, A., Languino, L. R., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-10-01
- Volume
- 25
- Issue
- 19
- Pages
- 8581-8591
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2156920440
- Cited by
- 312
- References
- 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Pratap, J., Javed, A., Languino, L. R., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2005). The Runx2 Osteogenic Transcription Factor Regulates Matrix Metalloproteinase 9 in Bone Metastatic Cancer Cells and Controls Cell Invasion. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.25.19.8581-8591.2005
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
