Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation Journal Article
| Authors: | Gao, H.; Chakraborty, G.; Lee-Lim, A. P.; Mavrakis, K. J.; Wendel, H. G.; Giancotti, F. G. |
| Article Title: | Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation |
| Abstract: | We have developed a screening platform for the isolation of genetic entities involved in metastatic reactivation. Retroviral libraries of cDNAs fromfully metastatic breast-cancer cells or pooled microRNAs were transduced into breast-cancer cells that become dormant upon infiltrating the lung. Upon inoculation in the tail vein of mice, the cells that had acquired the ability to undergo reactivation generated metastatic lesions. Integrated retroviral vectors were recovered from these lesions, sequenced, and subjected to a second round of validation. By using this strategy, we isolated canonical genes and microRNAs that mediate metastatic reactivation in the lung. To identify genes that oppose reactivation, we screened an expression library encoding shRNAs, and we identified target genes that encode potential enforcers of dormancy. Our screening strategy enables the identification and rapid biological validation of single genetic entities that are necessary to maintain dormancy or to induce reactivation. This technology should facilitate the elucidation of the molecular underpinnings of these processes. |
| Keywords: | controlled study; nonhuman; mouse; phenotype; animal tissue; mus; metastasis; microrna; gene expression; animal experiment; animal model; lung metastasis; gene activation; gene identification; cancer cell; breast carcinoma; retrovirus vector; bioinformatics; genetic screening; loss of function mutation; short hairpin rna; epithelial mesenchymal transition; dna library; gain of function mutation; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 111 |
| Issue: | 46 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2014-11-18 |
| Start Page: | 16532 |
| End Page: | 16537 |
| Language: | English |
| DOI: | 10.1073/pnas.1403234111 |
| PROVIDER: | scopus |
| PMCID: | PMC4246349 |
| PUBMED: | 25378704 |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2015 -- Source: Scopus |
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