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Cell Rep. 2017 Oct 10;21(2):495-507. doi: 10.1016/j.celrep.2017.09.057.

Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer.

Author information

1
Department of Neurologic Surgery, The Mayo Clinic, Jacksonville, FL, USA; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
3
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
4
Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
5
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
6
Department of Neurologic Surgery, The Mayo Clinic, Jacksonville, FL, USA.
7
Department of Biomedical Engineering and Systems Biology Institute, Yale University, New Haven, CT, USA. Electronic address: andre.levchenko@yale.edu.
8
Department of Neurologic Surgery, The Mayo Clinic, Jacksonville, FL, USA. Electronic address: quinones@mayo.edu.

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.

KEYWORDS:

YAP; brachyury; chordoma; glioblastoma; growth; lung carcinoma; stremness

PMID:
29020634
PMCID:
PMC5637538
DOI:
10.1016/j.celrep.2017.09.057
[Indexed for MEDLINE]
Free PMC Article

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