title: Tead2 expression levels control the subcellular distribution of Yap and Taz, zyxin expression and epithelial-mesenchymal transition.
abstract: The cellular changes during an epithelial-mesenchymal transition (EMT) largely rely on global changes in gene expression orchestrated by transcription factors. Tead transcription factors and their transcriptional co-activators Yap and Taz have been previously implicated in promoting an EMT; however, their direct transcriptional target genes and their functional role during EMT have remained elusive. We have uncovered a previously unanticipated role of the transcription factor Tead2 during EMT. During EMT in mammary gland epithelial cells and breast cancer cells, levels of Tead2 increase in the nucleus of cells, thereby directing a predominant nuclear localization of its co-factors Yap and Taz via the formation of Tead2-Yap-Taz complexes. Genome-wide chromatin immunoprecipitation and next generation sequencing in combination with gene expression profiling revealed the transcriptional targets of Tead2 during EMT. Among these, zyxin contributes to the migratory and invasive phenotype evoked by Tead2. The results demonstrate that Tead transcription factors are crucial regulators of the cellular distribution of Yap and Taz, and together they control the expression of genes critical for EMT and metastasis.
authors.affiliation: Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Maren
authors.initials: M
authors.lastname: Diepenbruck
authors.forename: Lorenz
authors.initials: L
authors.lastname: Waldmeier
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanek
authors.forename: Philipp
authors.initials: P
authors.lastname: Berninger
authors.forename: Phil
authors.initials: P
authors.lastname: Arnold
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000091102:YAP-Signaling Proteins; D060589:Zyxin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C486310:Tead2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C517794:Wwtr1 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D060589:Zyxin
keywords: Breast cancer; EMT; Taz; Tead; Yap; Zyxin; metastasis