ArticleCancer research2012
Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf-1 interaction as a novel target for metastatic disease.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 93 citations in OpenAlex.
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- The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling.Cell death & disease · 2023Article
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- A Novel PHD2/VHL-mediated Regulation of YAP1 Contributes to VEGF Expression and Angiogenesis.Cancer research communications · 2022Article
- Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.International journal of molecular sciences · 2021Review
- E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling.Development (Cambridge, England) · 2021Article
- Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.International journal of molecular sciences · 2020Review
- ZNF703 is Overexpressed in Papillary Thyroid Carcinoma Tissues and Mediates K1 Cell Proliferation.Pathology oncology research : POR · 2020Article
- Regulation of E2F1 activity via PKA-mediated phosphorylations.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
- Role of E2Fs and mitotic regulators controlled by E2Fs in the epithelial to mesenchymal transition.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues.Cells · 2019Review
- Article
- Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor CellsCancer research · 2019Article
- Knockdown of Golgi phosphoprotein 73 blocks the trafficking of matrix metalloproteinase-2 in hepatocellular carcinoma cells and inhibits cell invasion.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The retinoblastoma (Rb)-E2F transcriptional regulatory pathway plays a major role in cell-cycle regulation, but its role in invasion and metastasis is less well understood. We find that many genes involved in the invasion of cancer cells, such as matrix metalloproteinases (MMP), have potential E2F-binding sites in their promoters. E2F-binding sites were predicted on all 23 human MMP gene promoters, many of which harbored multiple E2F-binding sites. Studies presented here show that MMP genes such as MMP9, MMP14, and MMP15 which are overexpressed in non-small cell lung cancer, have multiple E2F-binding sites and are regulated by the Rb-E2F pathway. Chromatin immunoprecipitation assays showed the association of E2F1 with the MMP9, MMP14, and MMP15 promoters, and transient transfection experiments showed that these promoters are E2F responsive. Correspondingly, depletion of E2F family members by RNA interference techniques reduced the expression of these genes with a corresponding reduction in collagen degradation activity. Furthermore, activating Rb by inhibiting the interaction of Raf-1 with Rb by using the Rb-Raf-1 disruptor RRD-251 was sufficient to inhibit MMP transcription. This led to reduced invasion and migration of cancer cells in vitro and metastatic foci development in a tail vein lung metastasis model in mice. These results suggest that E2F transcription factors may play a role in promoting metastasis through regulation of MMP genes and that targeting the Rb-Raf-1 interaction is a promising approach for the treatment of metastatic 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.