Understanding molecular pathways and targets of brachyury in epithelial-mesenchymal transition (EMT) in human cancers

Song, Wenzhe and Gobe, Glenda C. (2016) Understanding molecular pathways and targets of brachyury in epithelial-mesenchymal transition (EMT) in human cancers. Current Cancer Drug Targets, 16 7: 586-593. doi:10.2174/1568009616666160328113338


Author Song, Wenzhe
Gobe, Glenda C.
Title Understanding molecular pathways and targets of brachyury in epithelial-mesenchymal transition (EMT) in human cancers
Journal name Current Cancer Drug Targets   Check publisher's open access policy
ISSN 1873-5576
1568-0096
Publication date 2016-09-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/1568009616666160328113338
Open Access Status Not yet assessed
Volume 16
Issue 7
Start page 586
End page 593
Total pages 8
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Language eng
Abstract 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.
Formatted abstract
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.
Keyword Brachyury
EMT
Epithelial-mesenchymal transition
Signal pathway
Transcription factor
Tumorigenesis
Vaccine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
Admin Only - School of Medicine
School of Medicine Publications
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 09 Oct 2016, 10:20:30 EST by System User on behalf of Learning and Research Services (UQ Library)