The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Regulation of Tumor Angiogenesis by EZH2
Open accessAbstract
SUMMARY While VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homologue 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (VASH1). EZH2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with EZH2 silencing in tumor cells. Collectively, these data support the potential for targeting EZH2 as an important therapeutic approach. SIGNIFICANCE In this work, we identify EZH2 as a key regulator of tumor angiogenesis. The increase in endothelial EZH2 is a direct result of VEGF stimulation and indicates the presence of a paracrine circuit that promotes angiogenesis. EZH2 silencing in the tumor-associated endothelial cells using siRNA, packaged in the chitosan delivery system, resulted in significant growth inhibition in an orthotopic ovarian cancer model. EZH2 silencing in tumor endothelial cells resulted in decreased angiogenesis that was mediated by increased levels of the angiogenesis inhibitor, vasohibin1 (VASH1). Combined, these data provide a significant conceptual advance in our understanding of the regulation of angiogenesis in ovarian carcinoma and support the potential for targeting EZH2 as a therapeutic approach.
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The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1933744100 · Cited by 1,649
Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
Thaker, P. H., Han, L. Y., Kamat, A. A., Arevalo, J. M., Takahashi, R., Lu, C., Jennings, N. B., Armaiz-Pena, G., Bankson, J. A., Ravoori, M., et al. (2006) · Nature Medicine · doi:10.1038/nm1447 · Cited by 1,320
Self-citationRapisarda, A., Hollingshead, M., Uranchimeg, B., Bonomi, C. A., Borgel, S. D., Carter, J. P., Gehrs, B., Raffeld, M., Kinders, R. J., Parchment, R., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0274 · Cited by 171
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Paraneoplastic thrombocytosis in ovarian cancer
Stone, R. L., Nick, A. M., McNeish, I. A., Balkwill, F., Han, H. D., Bottsford-Miller, J., Rupaimoole, R., Armaiz-Pena, G. N., Pecot, C. V., Coward, J., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1110352 · Cited by 812
Self-citationMaintaining cell identity: PRC2-mediated regulation of transcription and cancer
Comet, I., Riising, E. M., Leblanc, B., & Helin, K. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.83 · Cited by 432
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Metadata
- Authors
- Lu, C., Han, H. D., Mangala, L. S., Ali-Fehmi, R., Newton, C. S., Ozbun, L., Armaiz-Pena, G. N., Hu, W., Stone, R. L., Munkarah, A., Ravoori, M. K., Shahzad, M. M. K., Lee, J.-W., Mora, E., Langley, R. R., Carroll, A. R., Matsuo, K., Spannuth, W. A., Schmandt, R., Jennings, N. B., Goodman, B. W., Jaffe, R. B., Nick, A. M., Kim, H. S., Guven, E. O., Chen, Y.-H., Li, L.-Y., Hsu, M.-C., Coleman, R. L., Calin, G. A., Denkbas, E. B., Lim, J. Y., Lee, J.-S., Kundra, V., Birrer, M. J., Hung, M.-C., Lopez-Berestein, G., & Sood, A. K.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 18
- Issue
- 2
- Pages
- 185-197
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2152389213
- Cited by
- 399
- References
- 4
- FWCI
- 12.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Lu, C., Han, H. D., Mangala, L. S., Ali-Fehmi, R., Newton, C. S., Ozbun, L., Armaiz-Pena, G. N., Hu, W., Stone, R. L., Munkarah, A., Ravoori, M. K., Shahzad, M. M. K., Lee, J.-W., Mora, E., Langley, R. R., Carroll, A. R., Matsuo, K., Spannuth, W. A., Schmandt, R., . . . Sood, A. K. (2010). Regulation of Tumor Angiogenesis by EZH2. Cancer Cell. https://doi.org/10.1016/j.ccr.2010.06.016
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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