title: ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.
abstract: Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings.
authors.affiliation: Department of General and Visceral Surgery, University of Freiburg Medical Center, Hugstetter Strasse 55, 79106 Freiburg, Germany.|Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors.forename: Waltraut
authors.initials: W
authors.lastname: Lehmann
authors.affiliation: Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.|Institute for Biochemistry and Molecular Biology, ZMBZ, Albert-Ludwigs-University Freiburg, Stefan-Meier-Strasse 17, 91054 Freiburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mossmann
authors.affiliation: Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kleemann
authors.affiliation: Department of General and Visceral Surgery, University of Freiburg Medical Center, Hugstetter Strasse 55, 79106 Freiburg, Germany.|Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Mock
authors.affiliation: Institute for Biochemistry and Molecular Biology, ZMBZ, Albert-Ludwigs-University Freiburg, Stefan-Meier-Strasse 17, 91054 Freiburg, Germany.|BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.|Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan-Meier-Strasse 17, 91054 Freiburg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Brummer
authors.affiliation: Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Stefan-Meier-Strasse 17, 91054 Freiburg, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Herr
authors.affiliation: Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Brabletz
authors.affiliation: Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Stemmler
authors.affiliation: Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D000091102:YAP-Signaling Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1