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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2899-2906. Prepublished online as a Blood First Edition Paper on July 5, 2007; DOI 10.1182/blood-2007-01-064428. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-01-064428v1 110/8/2899    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shi, H. Articles by Luo, Y. Search for Related Content PubMed PubMed Citation Articles by Shi, H. Articles by Luo, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin Hubing Shi1, Yujie Huang1, Hao Zhou1, Xiaomin Song1, Shaopeng Yuan1, Yan Fu1, and Yongzhang Luo1 1 Laboratory of Protein Chemistry, the Protein Science Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, People's Republic of China The exact molecular mechanism of how endostatin inhibits angiogenesis and tumor growth remains uncharacterized. Here, we report that endostatin specifically binds to the cell surface nucleolin with high affinity. Blockage of nucleolin by a neutralizing antibody or knockdown of nucleolin by the RNA interference results in loss of antiendothelial activities of endostatin. Importantly, a neutralizing antinucleolin antibody abrogates the antiangiogenic and antitumor activities of endostatin in vivo. Nucleolin and endostatin are colocalized on the cell surface of endothelial cells of angiogenic blood vessels in the tumor environment. Finally, we found that endostatin is internalized and transported into cell nuclei of endothelial cell via nucleolin. In the nucleus, the phosphorylation of nucleolin, which is critical for cell proliferation, can be inhibited by endostatin. Our studies demonstrate that nucleolin is a novel functional receptor for endostatin, and mediates the antiangiogenic and antitumor activities of endostatin. These findings also provide mechanistic insights of how endostatin specifically inhibits proliferating endothelial cell growth and angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Endostatin finds a new partner: nucleolin Judah Folkman Blood 2007 110: 2786-2787. [Full Text] [PDF] This article has been cited by other articles: Y. Huang, N. Song, Y. Ding, S. Yuan, X. Li, H. Cai, H. Shi, and Y. Luo Pulmonary Vascular Destabilization in the Premetastatic Phase Facilitates Lung Metastasis Cancer Res., October 1, 2009; 69(19): 7529 - 7537. [Abstract] [Full Text] [PDF] N. Song, Y. Huang, H. Shi, S. Yuan, Y. Ding, X. Song, Y. Fu, and Y. Luo Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1{alpha}/CXCR4 Axis Cancer Res., August 1, 2009; 69(15): 6057 - 6064. [Abstract] [Full Text] [PDF] S. Yuan, Y. Fu, X. Wang, H. Shi, Y. Huang, X. Song, L. Li, N. Song, and Y. Luo Voltage-dependent anion channel 1 is involved in endostatin-induced endothelial cell apoptosis FASEB J, August 1, 2008; 22(8): 2809 - 2820. [Abstract] [Full Text] [PDF] V. Stepanova, T. Lebedeva, A. Kuo, S. Yarovoi, S. Tkachuk, S. Zaitsev, K. Bdeir, I. Dumler, M. S. Marks, Y. Parfyonova, et al. Nuclear translocation of urokinase-type plasminogen activator Blood, July 1, 2008; 112(1): 100 - 110. [Abstract] [Full Text] [PDF] R. N. Re and J. L. Cook The Basis of an Intracrine Pharmacology J. Clin. Pharmacol., March 1, 2008; 48(3): 344 - 350. [Abstract] [Full Text] [PDF]

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