Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency
The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to ente...
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| Format: | Article |
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American Association for Cancer Research (AACR)
2018
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| Online Access: | http://hdl.handle.net/1721.1/116965 https://orcid.org/0000-0002-3149-5128 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826208817523720192 |
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| author | Shibue, Tsukasa Dongre, Anushka Keckesova, Zuzana Reinhardt, Ferenc De Cock, Jasmine Morgan Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Shibue, Tsukasa Dongre, Anushka Keckesova, Zuzana Reinhardt, Ferenc De Cock, Jasmine Morgan Weinberg, Robert A |
| author_sort | Shibue, Tsukasa |
| collection | MIT |
| description | The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to enter latency and the cellular signals in the surrounding nonpermissive tissue microenvironment that maintain the latent state. However, relatively little is known about the mechanisms that enable disseminated tumor cells to escape cancer dormancy or tumor latency. We describe here an in vivo model of solitary metastatic latency in the lung parenchyma. The induction of a localized inflammation in the lungs, initiated by lipopolysaccharide treatment, triggers the awakening of these cells, which develop into macroscopic metastases. The escape from latency is dependent on the expression of Zeb1, a key regulator of the epithelial-to-mesenchymal transition (EMT). Furthermore, activation of the EMT program on its own, as orchestrated by Zeb1, is sufficient to incite metastatic out-growth by causing carcinoma cells to enter stably into a metastasis-initiating cell state. |
| first_indexed | 2024-09-23T14:12:48Z |
| format | Article |
| id | mit-1721.1/116965 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:12:48Z |
| publishDate | 2018 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1169652022-10-01T19:50:13Z Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency Shibue, Tsukasa Dongre, Anushka Keckesova, Zuzana Reinhardt, Ferenc De Cock, Jasmine Morgan Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) De Cock, Jasmine Morgan Weinberg, Robert A The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to enter latency and the cellular signals in the surrounding nonpermissive tissue microenvironment that maintain the latent state. However, relatively little is known about the mechanisms that enable disseminated tumor cells to escape cancer dormancy or tumor latency. We describe here an in vivo model of solitary metastatic latency in the lung parenchyma. The induction of a localized inflammation in the lungs, initiated by lipopolysaccharide treatment, triggers the awakening of these cells, which develop into macroscopic metastases. The escape from latency is dependent on the expression of Zeb1, a key regulator of the epithelial-to-mesenchymal transition (EMT). Furthermore, activation of the EMT program on its own, as orchestrated by Zeb1, is sufficient to incite metastatic out-growth by causing carcinoma cells to enter stably into a metastasis-initiating cell state. National Institutes of Health (U.S.) (Grant P01-CA080111) National Institutes of Health (U.S.) (Grant R01-CA078461) National Institutes of Health (U.S.) (Grant U54-CA163109) 2018-07-13T13:13:25Z 2018-07-13T13:13:25Z 2016-08 2016-06 2018-07-12T16:21:23Z Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 http://hdl.handle.net/1721.1/116965 De Cock, Jasmine M. et al. “Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency.” Cancer Research 76, 23 (August 2016): 6778–6784 © 2016 American Association for Cancer Research https://orcid.org/0000-0002-3149-5128 https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1158/0008-5472.CAN-16-0608 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC |
| spellingShingle | Shibue, Tsukasa Dongre, Anushka Keckesova, Zuzana Reinhardt, Ferenc De Cock, Jasmine Morgan Weinberg, Robert A Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title | Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title_full | Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title_fullStr | Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title_full_unstemmed | Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title_short | Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency |
| title_sort | inflammation triggers zeb1 dependent escape from tumor latency |
| url | http://hdl.handle.net/1721.1/116965 https://orcid.org/0000-0002-3149-5128 https://orcid.org/0000-0002-0895-3557 |
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