In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression
April 1, 2010
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2012
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| Online Access: | http://hdl.handle.net/1721.1/73630 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1811078707598589952 |
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| author | Ho, Emily E. Dubrovsky, Esther Gertler, Frank Meacham, Corbin Elizabeth Hemann, Michael |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ho, Emily E. Dubrovsky, Esther Gertler, Frank Meacham, Corbin Elizabeth Hemann, Michael |
| author_sort | Ho, Emily E. |
| collection | MIT |
| description | April 1, 2010 |
| first_indexed | 2024-09-23T11:04:11Z |
| format | Article |
| id | mit-1721.1/73630 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:04:11Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/736302022-10-01T00:57:16Z In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression Ho, Emily E. Dubrovsky, Esther Gertler, Frank Meacham, Corbin Elizabeth Hemann, Michael Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Ho, Emily E. Dubrovsky, Esther Gertler, Frank Meacham, Corbin Elizabeth Hemann, Michael April 1, 2010 Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies. National Institutes of Health (U.S.) (RO1 CA128803-01) Massachusetts Institute of Technology. Dept. of Biology (Training Grant) Massachusetts Institute of Technology. Undergraduate Research Opportunities Program National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967) 2012-10-04T20:30:51Z 2012-10-04T20:30:51Z 2009-09 2009-01 Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/73630 Meacham, Corbin E. et al. “In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression.” Nature Genetics 41.10 (2009): 1133–1137. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1038/ng.451 Nature Genetics Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Ho, Emily E. Dubrovsky, Esther Gertler, Frank Meacham, Corbin Elizabeth Hemann, Michael In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title | In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title_full | In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title_fullStr | In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title_full_unstemmed | In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title_short | In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression |
| title_sort | in vivo rnai screening identifies regulators of actin dynamics as key determinants of lymphoma progression |
| url | http://hdl.handle.net/1721.1/73630 https://orcid.org/0000-0003-3214-4554 |
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