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Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer
Invasion, metastasis and therapy resistance are the major cause of cancer‐associated deaths, and the EMT‐inducing transcription factor ZEB1 is a crucial stimulator of these processes. While work on ZEB1 has mainly focused on its role as a transcriptional repressor, it can also act as a transcription...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459422/ https://www.ncbi.nlm.nih.gov/pubmed/32692442 http://dx.doi.org/10.15252/embj.2019103209 |
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author | Feldker, Nora Ferrazzi, Fulvia Schuhwerk, Harald Widholz, Sebastian A Guenther, Kerstin Frisch, Isabell Jakob, Kathrin Kleemann, Julia Riegel, Dania Bönisch, Ulrike Lukassen, Sören Eccles, Rebecca L Schmidl, Christian Stemmler, Marc P Brabletz, Thomas Brabletz, Simone |
author_facet | Feldker, Nora Ferrazzi, Fulvia Schuhwerk, Harald Widholz, Sebastian A Guenther, Kerstin Frisch, Isabell Jakob, Kathrin Kleemann, Julia Riegel, Dania Bönisch, Ulrike Lukassen, Sören Eccles, Rebecca L Schmidl, Christian Stemmler, Marc P Brabletz, Thomas Brabletz, Simone |
author_sort | Feldker, Nora |
collection | PubMed |
description | Invasion, metastasis and therapy resistance are the major cause of cancer‐associated deaths, and the EMT‐inducing transcription factor ZEB1 is a crucial stimulator of these processes. While work on ZEB1 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‐wide ZEB1 binding study in triple‐negative breast cancer cells. We identified ZEB1 as a novel interactor of the AP‐1 factors FOSL1 and JUN and show that, together with the Hippo pathway effector YAP, they form a transactivation complex, predominantly activating tumour‐promoting genes, thereby synergising with its function as a repressor of epithelial genes. High expression of ZEB1, YAP, FOSL1 and JUN marks 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. |
format | Online Article Text |
id | pubmed-7459422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74594222020-09-03 Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer Feldker, Nora Ferrazzi, Fulvia Schuhwerk, Harald Widholz, Sebastian A Guenther, Kerstin Frisch, Isabell Jakob, Kathrin Kleemann, Julia Riegel, Dania Bönisch, Ulrike Lukassen, Sören Eccles, Rebecca L Schmidl, Christian Stemmler, Marc P Brabletz, Thomas Brabletz, Simone EMBO J Articles Invasion, metastasis and therapy resistance are the major cause of cancer‐associated deaths, and the EMT‐inducing transcription factor ZEB1 is a crucial stimulator of these processes. While work on ZEB1 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‐wide ZEB1 binding study in triple‐negative breast cancer cells. We identified ZEB1 as a novel interactor of the AP‐1 factors FOSL1 and JUN and show that, together with the Hippo pathway effector YAP, they form a transactivation complex, predominantly activating tumour‐promoting genes, thereby synergising with its function as a repressor of epithelial genes. High expression of ZEB1, YAP, FOSL1 and JUN marks 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. John Wiley and Sons Inc. 2020-07-21 2020-09-01 /pmc/articles/PMC7459422/ /pubmed/32692442 http://dx.doi.org/10.15252/embj.2019103209 Text en © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Feldker, Nora Ferrazzi, Fulvia Schuhwerk, Harald Widholz, Sebastian A Guenther, Kerstin Frisch, Isabell Jakob, Kathrin Kleemann, Julia Riegel, Dania Bönisch, Ulrike Lukassen, Sören Eccles, Rebecca L Schmidl, Christian Stemmler, Marc P Brabletz, Thomas Brabletz, Simone Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title | Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title_full | Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title_fullStr | Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title_full_unstemmed | Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title_short | Genome‐wide cooperation of EMT transcription factor ZEB1 with YAP and AP‐1 in breast cancer |
title_sort | genome‐wide cooperation of emt transcription factor zeb1 with yap and ap‐1 in breast cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459422/ https://www.ncbi.nlm.nih.gov/pubmed/32692442 http://dx.doi.org/10.15252/embj.2019103209 |
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