title: TEAD activity is restrained by MYC and stratifies human breast cancer subtypes.
abstract: c-Myc (MYC) is an oncogenic transcription factor that is commonly overexpressed in a wide variety of human tumors. In breast cancer, MYC has recently been linked to the triple-negative subtype, a subtype that lacks any targeted therapy. Previously, we demonstrated that MYC behaves as a potent repressor of YAP and TAZ, 2 transcriptional coactivators that function as downstream transducers of the Hippo pathway. In this previous study, MYC repressed YAP/TAZ not only in primary breast epithelial cells but also in mouse models of triple-negative tumors. Here, we extend our previous bioinformatic and experimental analyses and demonstrate that MYC deregulation in primary breast epithelial cells leads to a robust repression of TEAD transcription factor activity, the transcription factor family mainly responsible for YAP/TAZ recruitment. Surprisingly, we find that MYC and TEAD activity is able to stratify different breast cancer subtypes in large panels of breast cancer patients. Thus, a deep understanding of the MYC-YAP/TAZ circuitry might yield new insights into the establishment and maintenance of specific breast cancer subtypes.
authors.affiliation: a Leibniz Institute on Aging, Fritz Lipmann Institute e.V. , Jena , Germany.|b Theodor Boveri Institute, Biocenter, University of Würzburg , Würzburg Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Elster
authors.affiliation: b Theodor Boveri Institute, Biocenter, University of Würzburg , Würzburg Germany.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Jaenicke
authors.affiliation: b Theodor Boveri Institute, Biocenter, University of Würzburg , Würzburg Germany.|c Comprehensive Cancer Center Mainfranken, University of Würzburg , Würzburg , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.affiliation: a Leibniz Institute on Aging, Fritz Lipmann Institute e.V. , Jena , Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: von Eyss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: Breast Cancer; Hippo; MYC; Mammary Epithelial Cells; TAZ; TEAD; YAP