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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cheng, Xiaolong Shen, Zheng Yin, Litian Lu, Shih-hsin Cui, Yongping |
| Description | Author Affiliation: Cheng X ( Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, China.) |
| Abstract | ECRG2 is a novel gene that shows sequence similarity to KAZAL-type serine protease inhibitor. We have previously demonstrated that ECRG2 inhibits migration/invasion of lung cancer PG cells. However, the mechanism by which ECRG2 performs these activities is a compelling question. Urokinase-type plasmin activator (uPA) binding to uPAR induces migration/invasion through multiple interactors including integrins. In this study, we found that ECRG2 binds specifically to the kringle domain of uPA. Moreover, we demonstrated that ECRG2 forms a complex with uPA.uPAR, that such a complex modifies the dynamical association of uPAR with beta1 integrins, and that disruption inhibits Src/MAP (mitogen-activated protein) kinase pathway, resulting in suppression of cell migration/invasion in an in vitro Matrigel migration/invasion assay. Conversely, depletion of ECRG2 markedly enhanced the association of uPAR with beta1 integrins, elevated basal Src/MAP kinase activation, and stimulated HT1080, MDA-MB-231, and MCF-7 cell migration/invasion. Together, our results provide evidence that ECRG2 is involved in the regulation of migration/invasion through uPA/uPAR/beta1 integrins/Src/MAP kinase pathway and may represent a novel therapeutic target for cancer. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 45 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-11-06 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD29 Metabolism Cell Movement Neoplasms Physiopathology Receptors, Urokinase Plasminogen Activator Signal Transduction Tumor Suppressor Proteins Genetics Cell Line, Tumor Protein Binding Proteinase Inhibitory Proteins, Secretory Urokinase-Type Plasminogen Activator Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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