Chordoma Foundation

Brachyury

Review Article

Brachyury in Chordoma

  • Brachyury is highly expressed in all cells in nearly every chordoma tumor [cite source=’pubmed’]16538613[/cite]
  • Germ-line tandem duplication of the T (brachyury) gene causes familial chordoma [cite source=’pubmed’]19801981[/cite]
  • 97% of chordoma patients harbor at least one allele of the common nonsynonymous SNP rs2305089 in the brachyury gene [cite source=’pubmed’]23064415[/cite]
  • The brachyury gene is amplified in some sporadic chordomas [cite source=’pubmed’]21171078[/cite]
  • Knock down of brachyury in chordoma cell lines induces growth arrest and apoptosis [cite source=’pubmed’]21171078[/cite] [cite source=’pubmed’]21699479[/cite]

Brachyury in other Carcinomas

  • Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma [cite source=’pubmed’]23076115[/cite]
  • Brachyury protein was expressed in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the normal tissues evaluated in this study were negative for the expression of Brachyury protein. [cite source=’pubmed’]22611028[/cite]
  • The level of Brachyury expression corresponded to resistance of lung cancer cells to EGFR kinase inhibition. [cite source=’pubmed’]22611028[/cite]
  • Brachyury expression was associated with tumor stage in lung cancer [cite source=’pubmed’]20071775[/cite]
  • Brachyury mRNA expression in primary lung carcinoma tissues was a significant predictor of poor prognosis for 5-year disease-free survival and overall survival rates and was significantly correlated to vascular invasion, lymphatic permeation, histological grade, pathologic T stage, and pathologic N stage (P < 0.05). Brachyury mRNA expression was significantly inversely correlated to E-cadherin expression (P = 0.0252) and positively correlated to IL-8 protein (P = 0.0241) and to Slug protein (P = 0.0243) in adenocarcinoma tissues. [cite source=’pubmed’]23456319[/cite]
  • Brachyury confers cancer stem cell characteristics on colorectal cancer cells [cite source=’pubmed’]21365650[/cite]
  • Brachyury expression predicts poor prognosis at early stages of colorectal cancer. [cite source=’pubmed’]21220197[/cite]
  • Overexpression of Brachyury in human carcinoma cells induced changes characteristic of EMT, including upregulation of mesenchymal markers, downregulation of epithelial markers, and an increase in cell migration and invasion. Brachyury overexpression also repressed E-cadherin transcription, an effect partially mediated by Slug. Conversely, inhibition of Brachyury resulted in downregulation of mesenchymal markers and loss of cell migration and invasion and diminished the ability of human tumor cells to form lung metastases in a xenograft model. [cite source=’pubmed’]20071775[/cite]
  • Brachyury is a tumor-specific antigen. Brachyury expression was in found tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well as in cell lines derived from lung, colon, and prostate carcinomas, but not in the vast majority of the normal tissues tested. [cite source=’pubmed’]17438107[/cite]
  • Level of brachyury expression strongly correlates with degree of resistance to cytotoxic therapies (chemotherapy and radiation) in two in-vitro models of human lung carcinoma. [cite source=’pubmed’]23788039[/cite]
  • Chemotherapy treatment of lung carcinoma cells in vitro selects for cells that express high levels of brachyury, and treatment of tumor xenograft models selects for the growth of resistant tumors that express high levels of brachyury. Surviving cells and tumors in these in-vitro and in-vivo models exhibit lower growth rates. Brachyury overexpression is therefore suggested to inhibit the cell cycle by downregulating cyclin D, pRb, and p21, ultimately decreasing the susceptibility of tumor cells to cytotoxic therapies.  [cite source=’pubmed’]23788039[/cite]