Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers

Brachyury is an important transcription factor of the T-box gene family with an evolutionarily-conserved function in mesoderm development in the embryo. Recent research has demonstrated that, in various human carcinomas, overexpression of Brachyury is associated with epithelial-mesenchymal transition (EMT), tumor metastasis, expression of markers for cancer stem cells, and resistance to chemotherapy and radiotherapy. Brachyury is a diagnostic and prognostic biomarker, and its expression in tumor tissues is associated with increasing tumor grade, stage, invasiveness, metastasis and poor prognosis. Targeting of Brachyury-positive tumor cells may modulate the extent of EMT and stop invasiveness. Fibroblast growth factor, transforming growth factor-beta and other EMT signalling factors are involved in the molecular pathways of Brachyury in tumorigenesis and development. Experimentally, Brachyury knockdown resulted in downregulation of EMT and stem cell markers, formation of tumor spheroids, and invasiveness. Treatment with recombinant yeast-Brachyury vector-based vaccine can activate and expand Brachyury-specific CD4(+) and CD8(+) T-cells in vitro, with an outcome of lysis of human tumor cells expressing the Brachyury protein. Further understanding of the characteristics of Brachyury and its associated signaling pathways might help in developing novel therapeutic strategies against EMT.