Abstract
Molecular factors that define stem cell identity have recently emerged as oncogenic drivers. For instance, brachyury, a key developmental transcriptional factor, is also implicated in carcinogenesis, most notably of chordoma, through mechanisms that remain elusive. Here, we show that brachyury is a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury is mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. We further demonstrate that the brachyury-YAP regulatory pathway is associated with tumor aggressiveness. These results elucidate a mechanism of controlling both tumor stemness and aggressiveness through regulatory coupling of two developmental factors. Malignant neoplasms exhibit uninhibited and dysregulated growth coupled with acquisition of stem-like properties that are integral to the development and progression of disease. Shah et al. demonstrate a critical role of brachyury in regulating stemness and growth by activating YAP through direct transcriptional and post-transcriptional mechanisms in various cancers.
Original language | English (US) |
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Pages (from-to) | 495-507 |
Number of pages | 13 |
Journal | Cell reports |
Volume | 21 |
Issue number | 2 |
DOIs | |
State | Published - Oct 10 2017 |
Keywords
- YAP
- brachyury
- chordoma
- glioblastoma
- growth
- lung carcinoma
- stremness
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology