Genome-wide cooperation of EMT transcription factor ZEB1 with YAP and AP-1 in breast cancer

Abstract: 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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: The EMBO journal. - 39, 17 (2020) , e103209, ISSN: 1460-2075

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: 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 ; Brabletz, Thomas ; Brabletz, Simone

Weitere Informationen

• DOI: 10.15252/embj.2019103209
• URN: urn:nbn:de:bsz:25-freidok-2207113
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:24 MESZ