title: Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway.
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.
authors.affiliation: North West Cancer Research Institute, College of Natural Sciences, Bangor, Gwynedd, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Jezkova
authors.forename: Jason S
authors.initials: JS
authors.lastname: Williams
authors.forename: Ffion
authors.initials: F
authors.lastname: Jones-Hutchins
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sammut
authors.forename: Simon
authors.initials: S
authors.lastname: Gollins
authors.forename: Ian
authors.initials: I
authors.lastname: Cree
authors.forename: Sarah
authors.initials: S
authors.lastname: Coupland
authors.affiliation: North West Cancer Research Institute, College of Natural Sciences, Bangor, Gwynedd, UK; NISCHR Cancer Genetics Biomedical Research Unit, Welsh Government, Cathays Park, Cardiff, UK.
authors.forename: Ramsay J
authors.initials: RJ
authors.lastname: McFarlane
authors.affiliation: North West Cancer Research Institute, College of Natural Sciences, Bangor, Gwynedd, UK.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Wakeman
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D020825:T-Box Domain Proteins / Q000378:metabolism*; D014162:Transfection; D000098908:Brachyury Protein
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein