Oncotarget

Research Papers:

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

Jana Jezkova, Jason S. Williams, Filipe Pinto, Stephen J. Sammut, Geraint T. Williams, Simon Gollins, Ramsay J. McFarlane, Rui Manuel Reis and Jane A. Wakeman _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:11478-11486. https://doi.org/10.18632/oncotarget.7202

Metrics: PDF 1798 views  |   HTML 3308 views  |   ?  


Abstract

Jana Jezkova1,*, Jason S. Williams1,*, Filipe Pinto2,3, Stephen J. Sammut1, Geraint T. Williams4, Simon Gollins5, Ramsay J. McFarlane1,6, Rui Manuel Reis2,3,7, Jane A. Wakeman1

1North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor, UK

2Life and Health Sciences Research Institute (ICVS), School Health Sciences, University Minho, Braga, Portugal

3ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal

4Institute of Cancer and Genetics, Cardiff University Medical School, Cardiff, UK

5North Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board, Bodelwyddan, UK

6NISCHR Cancer Genetics Biomedical Research Unit, Cardiff, UK

7Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil

*These authors contributed equally to this work

Correspondence to:

Jane A. Wakeman, e-mail: [email protected]

Keywords: Brachyury, enteroendocrine cells, small intestine/colon, crypts, colorectal cancer

Received: September 16, 2015     Accepted: January 23, 2016     Published: February 05, 2016

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7202