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.
Keywords: Brachyury, epithelial-mesenchymal transition, EMT, transcription factor, tumorigenesis, signal pathway, vaccine.
Current Cancer Drug Targets
Title:Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers
Volume: 16 Issue: 7
Author(s): Wenzhe Song and Glenda C. Gobe
Affiliation:
Keywords: Brachyury, epithelial-mesenchymal transition, EMT, transcription factor, tumorigenesis, signal pathway, vaccine.
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.
Export Options
About this article
Cite this article as:
Song Wenzhe and Gobe C. Glenda, Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers, Current Cancer Drug Targets 2016; 16 (7) . https://dx.doi.org/10.2174/1568009616666160328113338
DOI https://dx.doi.org/10.2174/1568009616666160328113338 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Paeonol Inhibits Migration, Invasion and Bone Adhesion of Small Cell Lung Cancer Cells
Current Signal Transduction Therapy Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets Therapeutic Approach of Primary Bone Tumours by Bisphosphonates
Current Pharmaceutical Design Molecular Mechanisms of Thymoquinone as Anticancer Agent
Combinatorial Chemistry & High Throughput Screening Glucocorticoids Pharmacology: Past, Present and Future
Current Pharmaceutical Design Ewing’s Sarcoma Cancer Stem Cell Targeted Therapy
Current Stem Cell Research & Therapy Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy
Anti-Cancer Agents in Medicinal Chemistry Ectopic Thyroid Gland: Description of a Case and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting the Hedgehog Signaling Pathway with Small Molecules from Natural Sources
Current Medicinal Chemistry LncRNAs as Therapeutic Targets for Autophagy-involved Cardiovascular Diseases: A Review of Molecular Mechanism and T herapy Strategy
Current Medicinal Chemistry Interleukin-10 and Articular Cartilage: Experimental Therapeutical Approaches in Cartilage Disorders
Current Gene Therapy New Promises to Cure Cancer and Other Genetic Diseases/Disorders: Epi-drugs Through Epigenetics
Current Topics in Medicinal Chemistry MDM2 Increases Drug Resistance in Cancer Cells by Inducing EMT Independent of p53
Current Medicinal Chemistry Glucosamine Sulphate in Osteoarthritis: From Symptoms to Structure Modification
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Small-molecule Inhibitors of Epigenetic Mutations as Compelling Drugtargets for Myelodysplastic Syndromes
Current Cancer Drug Targets Editorial [Hot topic: Bisphosphonates and Bone Diseases: Past, Present and Future (Guest Editor: Dominique HEYMANN)]
Current Pharmaceutical Design Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy
Current Drug Targets New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors
Mini-Reviews in Medicinal Chemistry The Role of MDCT in Craniocervical Junction Pathologies: Pictorial Review
Current Medical Imaging