Genome-wide cooperation ofEMTtranscription factorZEB1 withYAPandAP-1 in breast cancer

Feldker N, Ferrazzi F, Schuhwerk H, Widholz SA, Guenther K, Frisch I, Jakob K, Kleemann J, Riegel D, Boenisch U, Lukassen S, Eccles R, Schmidl C, Stemmler M, Brabletz T, Brabletz S (2020)

Publication Type: Journal article

Publication year: 2020

Journal

EMBO Journal EMBO Press

Book Volume: 39

Journal Issue: 17

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.

Authors with CRIS profile

Nora Feldker Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Fulvia Ferrazzi Institute of Human Genetics Harald Schuhwerk Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Isabell Armstark Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Kathrin Fuchs Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Julia Kleemann Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Sören Lukassen Professur für Humangenetik Rebecca Eccles Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Marc Stemmler Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Simone Brabletz Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)

Involved external institutions

Universität Regensburg DE Germany (DE) Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE)

How to cite

APA:

Feldker, N., Ferrazzi, F., Schuhwerk, H., Widholz, S.A., Guenther, K., Frisch, I.,... Brabletz, S. (2020). Genome-wide cooperation ofEMTtranscription factorZEB1 withYAPandAP-1 in breast cancer. EMBO Journal, 39(17).

MLA:

Feldker, Nora, et al. "Genome-wide cooperation ofEMTtranscription factorZEB1 withYAPandAP-1 in breast cancer." EMBO Journal 39.17 (2020).

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