The T-box transcription factor Brachyury (T) has a well-established role in essential morphogenetic movements in the developing embryo, but in recent years has emerged as a cancer biomarker and promising therapeutic target. Studies in patientderived cancer tissues and cancer cells suggest that Brachyury is associated with poor patient survival and the epithelial to mesenchymal transition. These observations suggest that Brachyury has an important function in the progression of several cancers. However, the exact mechanism by which it is involved in cancer progression is still incompletely understood.
Here, we show that Brachyury has two expressed transcript variants (TV1 and TV2) that are expressed in both normal and cancer tissues. We report the expression of Brachyury in a subset of enteroendocrine cells (EECs) of the normal human colonic crypts, marked by the EEC marker Chromogranin A and occasionally by the reserve stem cell marker Lrig1. We hypothesise that these cells are a population of reserve stem cells in the normal colonic crypt and that Brachyury contributes to their maintenance and plastic response to damage and environmental cues. Brachyury positive EEC-like cells were observed in colorectal adenomas, primary colorectal cancers and metastases of colorectal origin. Furthermore, expression of Brachyury in EEC-like cells in primary colorectal carcinomas confers a poor survival outcome and progression-free survival in patients in which they are present.