| dc.contributor |
Massachusetts Institute of Technology. Department of Biology |
|
| dc.contributor |
Whitehead Institute for Biomedical Research |
|
| dc.contributor |
Hong, Sue-Jean |
|
| dc.contributor |
Bartel, David |
|
| dc.creator |
Title, Alexandra C. |
|
| dc.creator |
Pires, Nuno D. |
|
| dc.creator |
Hasenöhrl, Lynn |
|
| dc.creator |
Godbersen, Svenja |
|
| dc.creator |
Stokar-Regenscheit, Nadine |
|
| dc.creator |
Stoffel, Markus |
|
| dc.creator |
Hong, Sue-Jean |
|
| dc.creator |
Bartel, David |
|
| dc.date |
2019-03-12T13:54:06Z |
|
| dc.date |
2019-03-12T13:54:06Z |
|
| dc.date |
2018-11 |
|
| dc.date |
2018-04 |
|
| dc.date |
2019-03-04T14:02:13Z |
|
| dc.date.accessioned |
2023-03-01T18:12:11Z |
|
| dc.date.available |
2023-03-01T18:12:11Z |
|
| dc.identifier |
2041-1723 |
|
| dc.identifier |
http://hdl.handle.net/1721.1/120917 |
|
| dc.identifier |
Title, Alexandra C., Sue-Jean Hong, Nuno D. Pires, Lynn Hasenöhrl, Svenja Godbersen, Nadine Stokar-Regenscheit, David P. Bartel, and Markus Stoffel. “Genetic Dissection of the miR-200–Zeb1 Axis Reveals Its Importance in Tumor Differentiation and Invasion.” Nature Communications 9, no. 1 (November 7, 2018). © 2018 The Authors |
|
| dc.identifier |
https://orcid.org/0000-0002-3872-2856 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/279139 |
|
| dc.description |
The epithelial-to-mesenchymal transition (EMT) is an important mechanism for cancer progression and metastasis. Numerous in vitro and tumor-profiling studies point to the miR-200–Zeb1 axis as crucial in regulating this process, yet in vivo studies involving its regulation within a physiological context are lacking. Here, we show that miR-200 ablation in the Rip-Tag2 insulinoma mouse model induces beta-cell dedifferentiation, initiates an EMT expression program, and promotes tumor invasion. Strikingly, disrupting the miR-200 sites of the endogenous Zeb1 locus causes a similar phenotype. Reexpressing members of the miR-200 superfamily in vitro reveals that the miR-200c family and not the co-expressed and closely related miR-141 family is responsible for regulation of Zeb1 and EMT. Our results thus show that disrupting the in vivo regulation of Zeb1 by miR-200c is sufficient to drive EMT, thus highlighting the importance of this axis in tumor progression and invasion and its potential as a therapeutic target. |
|
| dc.description |
National Institute of General Medical Sciences (U.S.) |
|
| dc.format |
application/pdf |
|
| dc.publisher |
Nature Publishing Group |
|
| dc.relation |
http://dx.doi.org/10.1038/s41467-018-07130-z |
|
| dc.relation |
Nature Communications |
|
| dc.rights |
Creative Commons Attribution 4.0 International license |
|
| dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
|
| dc.source |
Nature |
|
| dc.title |
Genetic dissection of the miR-200–Zeb1 axis reveals its importance in tumor differentiation and invasion |
|
| dc.type |
Article |
|
| dc.type |
http://purl.org/eprint/type/JournalArticle |
|