TEAD activity is restrained by MYC and stratifies human breast cancer subtypes. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Elster, Dana; Jaenicke, Laura A.; Eilers, Martin; von Eyss, Björn
• Is Part Of: Cell cycle. Volume 15:Issue 19(2016)
• Page Start: 2551
• Page End: 2556
• Publication Date: 2016-10-01
• Subjects: Breast Cancer -- Hippo -- Mammary Epithelial Cells -- MYC -- TAZ -- TEAD -- YAP; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1207837
• Languages: English
• ISSNs: 1538-4101

Abstract

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.