title: Brachyury identifies a class of enteroendocrine cells in normal human intestinal crypts and colorectal cancer.
abstract: 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.
authors: North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
authors: Jana
authors: J
authors: Jezkova
authors: North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
authors: Jason S
authors: JS
authors: Williams
authors: Life and Health Sciences Research Institute (ICVS), School Health Sciences, University Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Filipe
authors: F
authors: Pinto
authors: North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
authors: Stephen J
authors: SJ
authors: Sammut
authors: Institute of Cancer and Genetics, Cardiff University Medical School, Cardiff, UK.
authors: Geraint T
authors: GT
authors: Williams
authors: North Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board, Bodelwyddan, UK.
authors: Simon
authors: S
authors: Gollins
authors: North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.|NISCHR Cancer Genetics Biomedical Research Unit, Cardiff, UK.
authors: Ramsay J
authors: RJ
authors: McFarlane
authors: Life and Health Sciences Research Institute (ICVS), School Health Sciences, University Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors: Rui Manuel
authors: RM
authors: Reis
authors: North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
authors: Jane A
authors: JA
authors: Wakeman
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
keywords: Brachyury; colorectal cancer; crypts; enteroendocrine cells; small intestine/colon