TY - JOUR

T1 - Brachyury regulates proliferation of cancer cells via a p27Kip1-dependent pathway

AU - Mcfarlane, R.J.

AU - Gollins, S.W.

AU - Wakeman, J.

AU - Jezkova, J.

AU - Williams, J.S.

AU - Jones-Hutchins, F.

AU - Sammut, S.J.

AU - Gollins, S.

AU - Cree, I.

AU - Coupland, S.

AU - McFarlane, R.J.

AU - Wakeman, J.A.

N1 - Cancer Research Wales; Tenovus; Coleg Cymraeg Cenedlaethol; National Institute for Social care and Health Research Academic Health Science collaboration; NWCRF (CR950) and Cancer Research Wales

PY - 2014/5/21

Y1 - 2014/5/21

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.1999

DO - 10.18632/oncotarget.1999

M3 - Article

VL - 5

SP - 3813

EP - 3822

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 11

ER -