EZH2 promotes a bi-lineage identity in basal-like breast cancer cells
The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differenti...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/80293 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826209481443246080 |
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| author | Granit, R. Z. Gabai, Y. Hadar, T. Karamansha, Y. Liberman, Leslie D. Waldhorn, I. Maly, B. Darash-Yahana, M. Peretz, T. Ben-Porath, Ittai Regev, Aviv Gat-Viks, Irit |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Granit, R. Z. Gabai, Y. Hadar, T. Karamansha, Y. Liberman, Leslie D. Waldhorn, I. Maly, B. Darash-Yahana, M. Peretz, T. Ben-Porath, Ittai Regev, Aviv Gat-Viks, Irit |
| author_sort | Granit, R. Z. |
| collection | MIT |
| description | The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition. |
| first_indexed | 2024-09-23T14:23:11Z |
| format | Article |
| id | mit-1721.1/80293 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:23:11Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/802932022-09-29T09:07:40Z EZH2 promotes a bi-lineage identity in basal-like breast cancer cells Granit, R. Z. Gabai, Y. Hadar, T. Karamansha, Y. Liberman, Leslie D. Waldhorn, I. Maly, B. Darash-Yahana, M. Peretz, T. Ben-Porath, Ittai Regev, Aviv Gat-Viks, Irit Massachusetts Institute of Technology. Department of Biology Regev, Aviv Regev, Aviv The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition. 2013-08-27T13:33:56Z 2013-08-27T13:33:56Z 2012-09 2012-07 Article http://purl.org/eprint/type/JournalArticle 0950-9232 1476-5594 http://hdl.handle.net/1721.1/80293 Granit, R Z, Y Gabai, T Hadar, Y Karamansha, L Liberman, I Waldhorn, I Gat-Viks, et al. “EZH2 promotes a bi-lineage identity in basal-like breast cancer cells.” Oncogene 32, no. 33 (September 17, 2012): 3886-3895. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1038/onc.2012.390 Oncogene Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group Regev via Courtney Crummett |
| spellingShingle | Granit, R. Z. Gabai, Y. Hadar, T. Karamansha, Y. Liberman, Leslie D. Waldhorn, I. Maly, B. Darash-Yahana, M. Peretz, T. Ben-Porath, Ittai Regev, Aviv Gat-Viks, Irit EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title | EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title_full | EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title_fullStr | EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title_full_unstemmed | EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title_short | EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| title_sort | ezh2 promotes a bi lineage identity in basal like breast cancer cells |
| url | http://hdl.handle.net/1721.1/80293 https://orcid.org/0000-0001-8567-2049 |
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