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Oncotarget. 2016 Mar 8;7(10):11478-86. doi: 10.18632/oncotarget.7202.

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

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North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
Life and Health Sciences Research Institute (ICVS), School Health Sciences, University Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Institute of Cancer and Genetics, Cardiff University Medical School, Cardiff, UK.
North Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board, Bodelwyddan, UK.
NISCHR Cancer Genetics Biomedical Research Unit, Cardiff, UK.
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.


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.


Brachyury; colorectal cancer; crypts; enteroendocrine cells; small intestine/colon

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