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Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway
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Jezkova, Jana, Williams, Jason S., Jones-Hutchins, Ffion, Sammut, Stephen J., Gollins, Simon, Cree, Ian A., Coupland, Sarah, McFarlane, Ramsay J. and Wakeman, Jane A. (2014) Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway. Oncotarget, Volume 5 (Number 11). pp. 3813-3822. ISSN 1949-2553.
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Official URL: http://www.impactjournals.com/oncotarget/index.php...
Abstract
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 Brachyury-positive colorectal cancer cells to proliferate and reduced levels of Brachyury result in inhibition of proliferation, with features consistent with the cells entering a quiescent-like 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: | Journal Article | ||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Transcription factors, Colon (Anatomy) -- Cancer, Rectum -- Cancer | ||||||||||
Journal or Publication Title: | Oncotarget | ||||||||||
Publisher: | Impact Journals LLC | ||||||||||
ISSN: | 1949-2553 | ||||||||||
Official Date: | 21 May 2014 | ||||||||||
Dates: |
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Volume: | Volume 5 | ||||||||||
Number: | Number 11 | ||||||||||
Number of Pages: | 10 | ||||||||||
Page Range: | pp. 3813-3822 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
Date of first compliant deposit: | 27 December 2015 | ||||||||||
Date of first compliant Open Access: | 27 December 2015 | ||||||||||
Funder: | Cancer Research Wales (CRW), Tenovus - The Cancer Charity, Coleg Cymraeg Cenedlaethol (CCC), National Institute for Social Care and Health Research (Wales) (NISCHR), North West Cancer Research Fund Institute (NWCRF) | ||||||||||
Grant number: | CR950 (NWCRF) |
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