Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling
Many tumors contain heterogeneous populations of cells, only some of which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer cells, often termed “cancer stem cells” or “cancer stem-like cells” (CSCs), rely upon developmental signa...
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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/1721.1/84629 https://orcid.org/0000-0002-9703-1780 |
| _version_ | 1811079620376657920 |
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| author | Gupta, Piyush Fillmore, Christine M. Rudnick, Jenny A. Caballero, Silvia Keller, Patricia J. Kuperwasser, Charlotte Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gupta, Piyush Fillmore, Christine M. Rudnick, Jenny A. Caballero, Silvia Keller, Patricia J. Kuperwasser, Charlotte Lander, Eric Steven |
| author_sort | Gupta, Piyush |
| collection | MIT |
| description | Many tumors contain heterogeneous populations of cells, only some of which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer cells, often termed “cancer stem cells” or “cancer stem-like cells” (CSCs), rely upon developmental signaling pathways that are important for survival and expansion of normal stem cells. Here we report that, in analogy to embryonic mammary epithelial biology, estrogen signaling expands the pool of functional breast CSCs through a paracrine FGF/FGFR/Tbx3 signaling pathway. Estrogen or FGF9 pretreatment induced CSC properties of breast cancer cell lines and freshly isolated breast cancer cells, whereas cotreatment of cells with tamoxifen or a small molecule inhibitor of FGFR signaling was sufficient to prevent the estrogen-induced expansion of CSCs. Furthermore, reduction of FGFR or Tbx3 gene expression was able to abrogate tumorsphere formation, whereas ectopic Tbx3 expression increased tumor seeding potential by 100-fold. These findings demonstrate that breast CSCs are stimulated by estrogen through a signaling pathway that similarly controls normal mammary epithelial stem cell biology. |
| first_indexed | 2024-09-23T11:17:57Z |
| format | Article |
| id | mit-1721.1/84629 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:17:57Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/846292022-10-01T02:39:30Z Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling Gupta, Piyush Fillmore, Christine M. Rudnick, Jenny A. Caballero, Silvia Keller, Patricia J. Kuperwasser, Charlotte Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Gupta, Piyush Lander, Eric S. Many tumors contain heterogeneous populations of cells, only some of which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer cells, often termed “cancer stem cells” or “cancer stem-like cells” (CSCs), rely upon developmental signaling pathways that are important for survival and expansion of normal stem cells. Here we report that, in analogy to embryonic mammary epithelial biology, estrogen signaling expands the pool of functional breast CSCs through a paracrine FGF/FGFR/Tbx3 signaling pathway. Estrogen or FGF9 pretreatment induced CSC properties of breast cancer cell lines and freshly isolated breast cancer cells, whereas cotreatment of cells with tamoxifen or a small molecule inhibitor of FGFR signaling was sufficient to prevent the estrogen-induced expansion of CSCs. Furthermore, reduction of FGFR or Tbx3 gene expression was able to abrogate tumorsphere formation, whereas ectopic Tbx3 expression increased tumor seeding potential by 100-fold. These findings demonstrate that breast CSCs are stimulated by estrogen through a signaling pathway that similarly controls normal mammary epithelial stem cell biology. 2014-01-31T19:06:11Z 2014-01-31T19:06:11Z 2010-11 2010-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/84629 Fillmore, C. M., P. B. Gupta, J. A. Rudnick, S. Caballero, P. J. Keller, E. S. Lander, and C. Kuperwasser. “Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling.” Proceedings of the National Academy of Sciences 107, no. 50 (December 14, 2010): 21737-21742. https://orcid.org/0000-0002-9703-1780 en_US http://dx.doi.org/10.1073/pnas.1007863107 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 | Gupta, Piyush Fillmore, Christine M. Rudnick, Jenny A. Caballero, Silvia Keller, Patricia J. Kuperwasser, Charlotte Lander, Eric Steven Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title | Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title_full | Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title_fullStr | Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title_full_unstemmed | Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title_short | Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling |
| title_sort | estrogen expands breast cancer stem like cells through paracrine fgf tbx3 signaling |
| url | http://hdl.handle.net/1721.1/84629 https://orcid.org/0000-0002-9703-1780 |
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