Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer

Publication date: 10 October 2017
Source:Cell Reports, Volume 21, Issue 2
Author(s): Sagar R. Shah, Justin M. David, Nathaniel D. Tippens, Ahmed Mohyeldin, Juan C. Martinez-Gutierrez, Sara Ganaha, Paula Schiapparelli, Duane H. Hamilton, Claudia Palena, Andre Levchenko, Alfredo Quiñones-Hinojosa
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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Teaser

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.


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