TY - JOUR

T1 - Brachyury identifies a class of enteroendocrine cells in normal human intestinal crypts and colorectal cancer

AU - Jezkova, J.

AU - Williams, J.S.

AU - Pinto, F.

AU - Sammut, S.J.

AU - Williams, G.T.

AU - Gollins, S.

AU - Mcfarlane, R.J.

AU - Reis, R.M.

AU - Wakeman, J.

N1 - NWCR (grant no. CR950); NISCHR AHSC; FCT; grant no. SFRH/BD/81369/2011; Brazilian National Counsel of Technological and Scientific Development (CNPq) scholarship; Wales Gene Park.

PY - 2016/2/5

Y1 - 2016/2/5

N2 - Normal homeostasis of adult intestinal epithelium and repair following tissue damage is maintained by a balance of stem and differentiated cells, many of which are still only poorly characterised. Enteroendocrine cells of the gut are a small population of differentiated, secretory cells that are critical for integrating nutrient sensing with metabolic responses, dispersed amongst other epithelial cells. Recent evidence suggests that sub-sets of secretory enteroendocrine cells can act as reserve stem cells. Given the link between cells with stem-like properties and cancer, it is important that we identify factors that might provide a bridge between the two. Here, we identify a sub-set of chromogranin A-positive enteroendocrine cells that are positive for the developmental and cancer-associated transcription factor Brachyury in normal human small intestinal and colonic crypts. Whilst chromogranin A-positive enteroendocrine cells are also Brachyury-positive in colorectal tumours, expression of Brachyury becomes more diffuse in these samples, suggesting a more widespread function in cancer. The finding of the developmental transcription factor Brachyury in normal adult human intestinal crypts may extend the functional complexity of enteroendocrine cells and serves as a platform for assessment of the molecular processes of intestinal homeostasis that underpins our understanding of human health, cancer and aging.

AB - Normal homeostasis of adult intestinal epithelium and repair following tissue damage is maintained by a balance of stem and differentiated cells, many of which are still only poorly characterised. Enteroendocrine cells of the gut are a small population of differentiated, secretory cells that are critical for integrating nutrient sensing with metabolic responses, dispersed amongst other epithelial cells. Recent evidence suggests that sub-sets of secretory enteroendocrine cells can act as reserve stem cells. Given the link between cells with stem-like properties and cancer, it is important that we identify factors that might provide a bridge between the two. Here, we identify a sub-set of chromogranin A-positive enteroendocrine cells that are positive for the developmental and cancer-associated transcription factor Brachyury in normal human small intestinal and colonic crypts. Whilst chromogranin A-positive enteroendocrine cells are also Brachyury-positive in colorectal tumours, expression of Brachyury becomes more diffuse in these samples, suggesting a more widespread function in cancer. The finding of the developmental transcription factor Brachyury in normal adult human intestinal crypts may extend the functional complexity of enteroendocrine cells and serves as a platform for assessment of the molecular processes of intestinal homeostasis that underpins our understanding of human health, cancer and aging.

U2 - 10.18632/oncotarget.7202

DO - 10.18632/oncotarget.7202

M3 - Article

VL - 2016

SP - 11478

EP - 11486

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 7

ER -