Feldker, Nora and Ferrazzi, Fulvia and Schuhwerk, Harald and Widholz, Sebastian A. and Guenther, Kerstin and Frisch, Isabell and Jakob, Kathrin and Kleemann, Julia and Riegel, Dania and Boenisch, Ulrike and Lukassen, Soeren and Eccles, Rebecca L. and Schmidl, Christian and Stemmler, Marc P. and Brabletz, Thomas and Brabletz, Simone (2020) Genome-wide cooperation ofEMTtranscription factorZEB1 withYAPandAP-1 in breast cancer. EMBO JOURNAL, 39 (17): e103209. ISSN 0261-4189, 1460-2075
Full text not available from this repository. (Request a copy)Abstract
Invasion, metastasis and therapy resistance are the major cause of cancer-associated deaths, and theEMT-inducing transcription factorZEB1 is a crucial stimulator of these processes. While work onZEB1 has mainly focused on its role as a transcriptional repressor, it can also act as a transcriptional activator. To further understand these two modes of action, we performed a genome-wideZEB1 binding study in triple-negative breast cancer cells. We identifiedZEB1 as a novel interactor of theAP-1 factorsFOSL1 andJUNand show that, together with the Hippo pathway effectorYAP, they form a transactivation complex, predominantly activating tumour-promoting genes, thereby synergising with its function as a repressor of epithelial genes. High expression ofZEB1,YAP,FOSL1 andJUNmarks the aggressive claudin-low subtype of breast cancer, indicating the translational relevance of our findings. Thus, our results link critical tumour-promoting transcription factors:ZEB1,AP-1 and Hippo pathway factors. Disturbing their molecular interaction may provide a promising treatment option for aggressive cancer types.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTOR ZEB1; EMT-ACTIVATOR ZEB1; PROMOTES METASTASIS; CELL PLASTICITY; CHIP-CHIP; EXPRESSION; GENE; REPRESSOR; PACKAGE; BINDING; AP-1; breast cancer; epithelial to mesenchymal transition; ZEB1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2021 07:30 |
| Last Modified: | 18 Mar 2021 07:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44184 |
Actions (login required)
 |
View Item |
