Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell migration, invasion, and metastasis
The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration bloc...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2015-03, Vol.75 (6), p.1102-1112 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | Pettersson, Filippa Del Rincon, Sonia V Emond, Audrey Huor, Bonnie Ngan, Elaine Ng, Jonathan Dobocan, Monica C Siegel, Peter M Miller, Jr, Wilson H |
| description | The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration blocked the growth of primary breast tumors in several murine models and reduced the development of lung metastases in an invasive model. Mechanistically, eIF4E silencing or blockade reduced the invasiveness and metastatic capability of breast cancer cells in a manner associated with decreased activity of matrix metalloproteinase (MMP)-3 and MMP-9. Furthermore, eIF4E silencing or ribavirin treatment suppressed features of epithelial-to-mesenchymal transition, a process crucial for metastasis. Our findings offer a preclinical rationale to explore broadening the clinical evaluation of ribavirin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors such as metastatic breast cancer. |
| doi_str_mv | 10.1158/0008-5472.CAN-14-1996 |
| format | Article |
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Our findings offer a preclinical rationale to explore broadening the clinical evaluation of ribavirin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors such as metastatic breast cancer.</description><subject>Animals</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Eukaryotic Initiation Factor-4E - antagonists & inhibitors</subject><subject>Eukaryotic Initiation Factor-4E - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - secondary</subject><subject>Matrix Metalloproteinase 9 - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Invasiveness</subject><subject>Ribavirin - therapeutic use</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1PAjEQhhujEUR_gqZHDy62248tR0IASYhe9Ny03VlYsx_Y7pr47-0Kcmpn8rzT6YPQPSVTSoV6JoSoRPAsnS7mrwnlCZ3N5AUaU8FUknEuLtH4zIzQTQifsRSUiGs0SoUkKqNkjKo1NNCVDpsmx4e98bVxbdXuYqds9qUtu7JtcFtg2Kz4EnvIewcBWw8mdNiZxoHHDqoK1-XOm4F-islvE_5uw9QausjGRrhFV4WpAtydzgn6WC3fFy_J9m29Wcy3iWNCdonj-UxaEZe1lhMmuOMqLbiUxjGpAHieplJZ4ozJSCyk4sa4PH5W5NbajE3Q43HuwbdfPYRO12UYljQNtH3QVEqmZirjLKLiiDrfhuCh0Adf1sb_aEr0IFoPEvUgUUfRmnI9iI65h9MTva0hP6f-zbJfnjN6DQ</recordid><startdate>20150315</startdate><enddate>20150315</enddate><creator>Pettersson, Filippa</creator><creator>Del Rincon, Sonia V</creator><creator>Emond, Audrey</creator><creator>Huor, Bonnie</creator><creator>Ngan, Elaine</creator><creator>Ng, Jonathan</creator><creator>Dobocan, Monica C</creator><creator>Siegel, Peter M</creator><creator>Miller, Jr, Wilson H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150315</creationdate><title>Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell migration, invasion, and metastasis</title><author>Pettersson, Filippa ; 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| ispartof | Cancer research (Chicago, Ill.), 2015-03, Vol.75 (6), p.1102-1112 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animals Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Line, Tumor Cell Movement Epithelial-Mesenchymal Transition Eukaryotic Initiation Factor-4E - antagonists & inhibitors Eukaryotic Initiation Factor-4E - genetics Female Humans Lung Neoplasms - secondary Matrix Metalloproteinase 9 - physiology Mice Mice, Inbred BALB C Neoplasm Invasiveness Ribavirin - therapeutic use Transforming Growth Factor beta - pharmacology |
| title | Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell migration, invasion, and metastasis |
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