Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes
The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the EMT include several transcription factors (TFs), such as Goosecoid, Snail, and...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/84510 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-9703-1780 |
| _version_ | 1811076514994716672 |
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| author | Taube, Joseph H. Herschkowitz, Jason I. Komurov, Kakajan Zhou, Alicia Y. Gupta, Supriya Yang, Jing Hartwell, Kimberly A. Gupta, Piyush Evans, Kurt W. Hollier, Brett G. Ram, Prahlad T. Rosen, Jeffrey M. Mani, Sendurai A. Onder, Tamer T Lander, Eric Steven Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Taube, Joseph H. Herschkowitz, Jason I. Komurov, Kakajan Zhou, Alicia Y. Gupta, Supriya Yang, Jing Hartwell, Kimberly A. Gupta, Piyush Evans, Kurt W. Hollier, Brett G. Ram, Prahlad T. Rosen, Jeffrey M. Mani, Sendurai A. Onder, Tamer T Lander, Eric Steven Weinberg, Robert A |
| author_sort | Taube, Joseph H. |
| collection | MIT |
| description | The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the EMT include several transcription factors (TFs), such as Goosecoid, Snail, and Twist, as well as the secreted TGF-β1. Each of these factors is capable, on its own, of inducing an EMT in the human mammary epithelial (HMLE) cell line. However, the interactions between these regulators are poorly understood. Overexpression of each of the above EMT inducers up-regulates a subset of other EMT-inducing TFs, with Twist, Zeb1, Zeb2, TGF-β1, and FOXC2 being commonly induced. Up-regulation of Slug and FOXC2 by either Snail or Twist does not depend on TGF-β1 signaling. Gene expression signatures (GESs) derived by overexpressing EMT-inducing TFs reveal that the Twist GES and Snail GES are the most similar, although the Goosecoid GES is the least similar to the others. An EMT core signature was derived from the changes in gene expression shared by up-regulation of Gsc, Snail, Twist, and TGF-β1 and by down-regulation of E-cadherin, loss of which can also trigger an EMT in certain cell types. The EMT core signature associates closely with the claudin-low and metaplastic breast cancer subtypes and correlates negatively with pathological complete response. Additionally, the expression level of FOXC1, another EMT inducer, correlates strongly with poor survival of breast cancer patients. |
| first_indexed | 2024-09-23T10:23:24Z |
| format | Article |
| id | mit-1721.1/84510 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:23:24Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/845102022-09-26T17:33:57Z Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes Taube, Joseph H. Herschkowitz, Jason I. Komurov, Kakajan Zhou, Alicia Y. Gupta, Supriya Yang, Jing Hartwell, Kimberly A. Gupta, Piyush Evans, Kurt W. Hollier, Brett G. Ram, Prahlad T. Rosen, Jeffrey M. Mani, Sendurai A. Onder, Tamer T Lander, Eric Steven Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Zhou, Alicia Y. Onder, Tamer T. Gupta, Piyush Lander, Eric S. Weinberg, Robert A. The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the EMT include several transcription factors (TFs), such as Goosecoid, Snail, and Twist, as well as the secreted TGF-β1. Each of these factors is capable, on its own, of inducing an EMT in the human mammary epithelial (HMLE) cell line. However, the interactions between these regulators are poorly understood. Overexpression of each of the above EMT inducers up-regulates a subset of other EMT-inducing TFs, with Twist, Zeb1, Zeb2, TGF-β1, and FOXC2 being commonly induced. Up-regulation of Slug and FOXC2 by either Snail or Twist does not depend on TGF-β1 signaling. Gene expression signatures (GESs) derived by overexpressing EMT-inducing TFs reveal that the Twist GES and Snail GES are the most similar, although the Goosecoid GES is the least similar to the others. An EMT core signature was derived from the changes in gene expression shared by up-regulation of Gsc, Snail, Twist, and TGF-β1 and by down-regulation of E-cadherin, loss of which can also trigger an EMT in certain cell types. The EMT core signature associates closely with the claudin-low and metaplastic breast cancer subtypes and correlates negatively with pathological complete response. Additionally, the expression level of FOXC1, another EMT inducer, correlates strongly with poor survival of breast cancer patients. National Institutes of Health (U.S.) (Grant R01 CA78461) Breast Cancer Research Foundation Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology 2014-01-24T18:42:54Z 2014-01-24T18:42:54Z 2010-08 2010-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/84510 Taube, J. H., J. I. Herschkowitz, K. Komurov, A. Y. Zhou, S. Gupta, J. Yang, K. Hartwell, et al. “Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes.” Proceedings of the National Academy of Sciences 107, no. 35 (August 31, 2010): 15449-15454. https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-9703-1780 en_US http://dx.doi.org/10.1073/pnas.1004900107 Proceedings of the National Academy of Sciences 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 National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Taube, Joseph H. Herschkowitz, Jason I. Komurov, Kakajan Zhou, Alicia Y. Gupta, Supriya Yang, Jing Hartwell, Kimberly A. Gupta, Piyush Evans, Kurt W. Hollier, Brett G. Ram, Prahlad T. Rosen, Jeffrey M. Mani, Sendurai A. Onder, Tamer T Lander, Eric Steven Weinberg, Robert A Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title | Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title_full | Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title_fullStr | Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title_full_unstemmed | Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title_short | Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes |
| title_sort | core epithelial to mesenchymal transition interactome gene expression signature is associated with claudin low and metaplastic breast cancer subtypes |
| url | http://hdl.handle.net/1721.1/84510 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0002-9703-1780 |
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