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-β 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.
Keywords: Brachyury, epithelial-mesenchymal transition, EMT, transcription factor, tumorigenesis, signal pathway, vaccine.
Rights & PermissionsPrintExport