Journal
CELL REPORTS
Volume 21, Issue 2, Pages 495-507Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.057
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Funding
- National Science Foundation
- NIH National Cancer Institute (NCI) [U54-CA209992]
- NIH [R01 NS070024]
- Center for Cancer Research, NCI, NIH
- Chordoma Foundation
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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.
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