Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast
The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness, and self-renewal traits. During both normal development and tumor pathogenesis, this change in cell phenotype is induced by contextual signals that epithelial cells receive from their micr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92261 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826216652453183488 |
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| author | Scheel, Christina Eaton, Elinor Ng Chaffer, Christine L. Reinhardt, Ferenc Kah, Kong-Jie Bell, George Guo, Wenjun Rubin, Jeffrey Richardson, Andrea L. Weinberg, Robert A. Li, Sophia Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Scheel, Christina Eaton, Elinor Ng Chaffer, Christine L. Reinhardt, Ferenc Kah, Kong-Jie Bell, George Guo, Wenjun Rubin, Jeffrey Richardson, Andrea L. Weinberg, Robert A. Li, Sophia Weinberg, Robert A |
| author_sort | Scheel, Christina |
| collection | MIT |
| description | The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness, and self-renewal traits. During both normal development and tumor pathogenesis, this change in cell phenotype is induced by contextual signals that epithelial cells receive from their microenvironment. The signals that are responsible for inducing an EMT and maintaining the resulting cellular state have been unclear. We describe three signaling pathways, involving transforming growth factor (TGF)-β and canonical and noncanonical Wnt signaling, that collaborate to induce activation of the EMT program and thereafter function in an autocrine fashion to maintain the resulting mesenchymal state. Downregulation of endogenously synthesized inhibitors of autocrine signals in epithelial cells enables the induction of the EMT program. Conversely, disruption of autocrine signaling by added inhibitors of these pathways inhibits migration and self-renewal in primary mammary epithelial cells and reduces tumorigenicity and metastasis by their transformed derivatives. |
| first_indexed | 2024-09-23T16:50:54Z |
| format | Article |
| id | mit-1721.1/92261 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:50:54Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/922612022-10-03T08:41:51Z Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast Scheel, Christina Eaton, Elinor Ng Chaffer, Christine L. Reinhardt, Ferenc Kah, Kong-Jie Bell, George Guo, Wenjun Rubin, Jeffrey Richardson, Andrea L. Weinberg, Robert A. Li, Sophia Weinberg, Robert A Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) Li, Sophia Kah, Kong-Jie Weinberg, Robert A. The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness, and self-renewal traits. During both normal development and tumor pathogenesis, this change in cell phenotype is induced by contextual signals that epithelial cells receive from their microenvironment. The signals that are responsible for inducing an EMT and maintaining the resulting cellular state have been unclear. We describe three signaling pathways, involving transforming growth factor (TGF)-β and canonical and noncanonical Wnt signaling, that collaborate to induce activation of the EMT program and thereafter function in an autocrine fashion to maintain the resulting mesenchymal state. Downregulation of endogenously synthesized inhibitors of autocrine signals in epithelial cells enables the induction of the EMT program. Conversely, disruption of autocrine signaling by added inhibitors of these pathways inhibits migration and self-renewal in primary mammary epithelial cells and reduces tumorigenicity and metastasis by their transformed derivatives. National Cancer Institute (U.S.) (CA12515) National Cancer Institute (U.S.) (DE020817) Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology Breast Cancer Research Foundation Dana-Farber/Harvard Cancer Center. SPORE United States. Dept. of Defense. Congressionally Directed Medical Research Programs. Breast Cancer Research Program (Idea Award) Samuel Waxman Foundation 2014-12-10T19:33:28Z 2014-12-10T19:33:28Z 2011-06 2011-02 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/92261 Scheel, Christina, Elinor Ng Eaton, Sophia Hsin-Jung Li, Christine L. Chaffer, Ferenc Reinhardt, Kong-Jie Kah, George Bell, et al. “Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast.” Cell 145, no. 6 (June 2011): 926–940. © 2011 Elsevier Inc. https://orcid.org/0000-0002-0895-3557 en_US http://dx.doi.org/10.1016/j.cell.2011.04.029 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 Elsevier |
| spellingShingle | Scheel, Christina Eaton, Elinor Ng Chaffer, Christine L. Reinhardt, Ferenc Kah, Kong-Jie Bell, George Guo, Wenjun Rubin, Jeffrey Richardson, Andrea L. Weinberg, Robert A. Li, Sophia Weinberg, Robert A Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title | Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title_full | Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title_fullStr | Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title_full_unstemmed | Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title_short | Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast |
| title_sort | paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast |
| url | http://hdl.handle.net/1721.1/92261 https://orcid.org/0000-0002-0895-3557 |
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