MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis

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题名:	MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis
作者:	王陸海;Chan, S-H;Huang, W-C;Chang, J-W;Chang, K-J;Kuo, W-H;Wang, M-Y;Lin, K-Y;Uen, Y-H;Hou, M-F;Lin, C-M;Jang, T-H;Tu, C-W;Lee, Y-R;Lee, Y-H;Tien, M-T;Wang, L-H
贡献者:	生醫理工學院生命科學系
关键词:	631/337/384/331;631/80/86;692/699/67/1347;692/699/67/322;Adaptor Proteins, Signal Transducing - genetics;Adaptor Proteins, Signal Transducing - metabolism;Apoptosis;Breast cancer;Breast Neoplasms - metabolism;Breast Neoplasms - pathology;Cell adhesion & migration;Cell Biology;Cell Cycle Proteins - genetics;Cell Cycle Proteins - metabolism;Development and progression;Female;Gene Expression Regulation, Neoplastic;Gene Knockdown Techniques;Genetic aspects;Human Genetics;Humans;Integrins;Integrins - genetics;Integrins - metabolism;Internal Medicine;Medicine;Medicine & Public Health;Metastasis;MicroRNA;MicroRNAs;MicroRNAs - genetics;MicroRNAs - metabolism;Neoplasm Invasiveness - pathology;Neoplasm Metastasis - pathology;Oncology;Original;original-article;Properties;Signal Transduction;Tumor Cells, Cultured
日期:	2014-09-04
上传时间:	2026-04-23 11:13:24 (UTC+8)
出版者:	Nature Publishing Group;London: Springer Science and Business Media LLC
摘要:	摘要： Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics. 其他題名： Oncogene 出版者： London: Springer Science and Business Media LLC 出版日期： 2014-09-04 出處： Oncogene, 2014-09, Vol.33 (36), p.4496-4507 資源來源： EBSCOhost Academic Search Premier 版權： The Author(s) 2014 版權： COPYRIGHT 2014 Nature Publishing Group 版權： Copyright Nature Publishing Group Sep 4, 2014 版權： Copyright © 2014 Macmillan Publishers Limited 2014 Macmillan Publishers Limited 識別號： ISSN: 0950-9232 識別號： ISSN: 1476-5594 識別號： EISSN: 1476-5594 識別號： DOI: 10.1038/onc.2014.10 識別號： PMID: 24608434 識別號： CODEN: ONCNES
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