期刊
ONCOTARGET
卷 7, 期 10, 页码 11478-11486出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7202
关键词
Brachyury; enteroendocrine cells; small intestine/colon; crypts; colorectal cancer
资金
- Cancer Research Wales
- Coleg Cymraeg Cenedlaethol
- NWCR [CR950]
- National Institute for Social Care and Health Research Academic Health Science Collaboration (NISCHR AHSC)
- Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/81369/2011]
- Brazilian National Counsel of Technological and Scientific Development (CNPq) scholarship
- Wales Gene Park
- Fundação para a Ciência e a Tecnologia [SFRH/BD/81369/2011] Funding Source: FCT
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.
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