A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis
MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose ex...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96204 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826216116333051904 |
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| author | Valastyan, Scott John Reinhardt, Ferenc Benaich, Nathan Calogrias, Diana Szász, Attila M. Wang, Zhigang C. Brock, Jane E. Richardson, Andrea L. Nathan Benaich Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Valastyan, Scott John Reinhardt, Ferenc Benaich, Nathan Calogrias, Diana Szász, Attila M. Wang, Zhigang C. Brock, Jane E. Richardson, Andrea L. Nathan Benaich Weinberg, Robert A |
| author_sort | Valastyan, Scott John |
| collection | MIT |
| description | MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis. |
| first_indexed | 2024-09-23T16:42:35Z |
| format | Article |
| id | mit-1721.1/96204 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:42:35Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/962042022-09-29T20:56:44Z A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis Valastyan, Scott John Reinhardt, Ferenc Benaich, Nathan Calogrias, Diana Szász, Attila M. Wang, Zhigang C. Brock, Jane E. Richardson, Andrea L. Nathan Benaich Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Valastyan, Scott John Reinhardt, Ferenc Nathan Benaich Weinberg, Robert A. MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis. Massachusetts Institute of Technology (Daniel K. Ludwig Foundation Cancer Research Professor) American Cancer Society (ACS Research Professor) United States. Dept. of Defense (Breast Cancer Research Program Predoctoral Fellow) United States. Dept. of Defense (Breast Cancer Research Program, DoD BCRP Idea Award)) Harvard University (Harvard Breast Cancer SPORE) National Institutes of Health (U.S.) (RO1 CA078461) National Institutes of Health (U.S.) (PO1 CA080111) 2015-03-26T20:31:15Z 2015-03-26T20:31:15Z 2009-06 2009-01 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/96204 Valastyan, Scott, Ferenc Reinhardt, Nathan Benaich, Diana Calogrias, Attila M. Szász, Zhigang C. Wang, Jane E. Brock, Andrea L. Richardson, and Robert A. Weinberg. “A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis.” Cell 137, no. 6 (June 2009): 1032–1046. © 2009 Elsevier Inc. https://orcid.org/0000-0002-0895-3557 en_US http://dx.doi.org/10.1016/j.cell.2009.03.047 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Valastyan, Scott John Reinhardt, Ferenc Benaich, Nathan Calogrias, Diana Szász, Attila M. Wang, Zhigang C. Brock, Jane E. Richardson, Andrea L. Nathan Benaich Weinberg, Robert A A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title | A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title_full | A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title_fullStr | A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title_full_unstemmed | A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title_short | A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis |
| title_sort | pleiotropically acting microrna mir 31 inhibits breast cancer metastasis |
| url | http://hdl.handle.net/1721.1/96204 https://orcid.org/0000-0002-0895-3557 |
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