Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway

Jezkova, J. and Williams, J.S. and Jones-Hutchins, F. and Sammut, S.J. and Gollins, S. and Cree, I. and Coupland, S. and McFarlane, R.J. and Wakeman, J.A. (2014) Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway. Oncotarget, 5 ((11)). pp. 3813-3822. DOI: doi:10.18632/oncotarget.1999

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The T-box transcription factor Brachyury is expressed in a number of tumour types and has been demonstrated to have cancer inducing properties. To date, it has been linked to cancer associated induction of epithelial to mesenchymal transition, tumour metastasis and expression of markers for cancer stem-like cells. Taken together, these findings indicate that Brachyury plays an important role in the progression of cancer, although the mechanism through which it functions is poorly understood. Here we show that Brachyury regulates the potential of Brachyurypositive colorectal cancer cells to proliferate and reduced levels of Brachyury result in inhibition of proliferation, with features consistent with the cells entering a quiescentlike state. This inhibition of proliferation is dependent upon p27Kip1 demonstrating that Brachyury acts to modulate cellular proliferative fate in colorectal cancer cells in a p27Kip1-dependent manner. Analysis of patient derived colorectal tumours reveals a heterogeneous localisation of Brachyury (in the nucleolus, nucleus and cytoplasm) indicating the potential complexity of the regulatory role of Brachyury in solid colorectal tumours.

Item Type: Article
Subjects: Research Publications
Departments: College of Natural Sciences > School of Biological Sciences
College of Health and Behavioural Sciences > School of Medical Sciences
Date Deposited: 09 Dec 2014 16:29
Last Modified: 09 Apr 2016 02:34
ISSN: 1949-2553
URI: http://e.bangor.ac.uk/id/eprint/298
Identification Number: DOI: doi:10.18632/oncotarget.1999
Publisher: Impact Journals
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