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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.

Author information

1
North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK.
2
Life and Health Sciences Research Institute (ICVS), School Health Sciences, University Minho, Braga, Portugal.
3
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
4
Institute of Cancer and Genetics, Cardiff University Medical School, Cardiff, UK.
5
North Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board, Bodelwyddan, UK.
6
NISCHR Cancer Genetics Biomedical Research Unit, Cardiff, UK.
7
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.

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.

KEYWORDS:

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

PMID:
26862851
PMCID:
PMC4905487
DOI:
10.18632/oncotarget.7202
[Indexed for MEDLINE]
Free PMC Article

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