T-box transcription factor Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma

Abstract

The prognosis of patients with oral squamous cell carcinoma (SCC) is influenced by the presence of lymph node metastasis. Epithelial-mesenchymal transition (EMT), a process that involves events that convert adherent epithelial cells into individual migratory cells that can invade the extracellular matrix, is critical for cancer progression. Recently, the T-box transcription factor Brachyury was reported to promote EMT in human carcinoma cell lines. We analyzed the relationship between EMT (assessed by staining for E-cadherin and Vimentin) and the expression of Brachyury in association with lymph node metastasis in oral SCC. Oral SCC biopsy specimens (152 cases) were examined immunohistochemically for the expression of E-cadherin, Vimentin and Brachyury. Expression of Brachyury was correlated with EMT (p=0.035) and was significantly associated with lymph node and distant metastasis (p<0.05). Logistic regression analysis showed that Brachyury and EMT were predictive factors for lymph node metastasis (odds ratio 4.390 and 5.936, respectively) and that EMT was a predictive factor for distant metastases (odds ratio 11.786). Our findings present clinical evidence for an important role of Brachyury in EMT in oral SCC, and suggest that Brachyury and EMT patterns are useful prognostic markers.

Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma

“…These results are consistent with those of previous studies, which revealed that silencing brachyury expression inhibits tumor formation and metastasis in human adenoid cystic carcinoma cells (19,20). In addition, a previous study revealed that brachyury expression is associated with EMT and lymph node metastasis in OSCC patients (22).…”

“…Recently, the T-box transcription factor brachyury, which is essential for mesoderm formation during early development (16,17), has been found to regulate the epithelial-mesenchymal transition (EMT) and CSC potential in human salivary carcinoma cells (18)(19)(20)(21). In addition, brachyury expression was found to correlate with lymph node metastasis in OSCC (22). However, to date, the association between SOX2, Oct4, KLF4, c-Myc and brachyury expression in OSCC has not been investigated.…”

SMC1 promotes epithelial-mesenchymal transition in triple-negative breast cancer through upregulating Brachyury

“…A previous study reported that Brachyury was highly expressed in human tumor cells, but not in the corresponding normal cell lines (29). Fernando et al reported that Brachyury could induce EMT in human epithelial cells through the repression of E-cadherin and the induction of Slug (31).…”

“…Briefly, during the EMT process, cells may lose epithelial markers and adherent ability, and gain mesenchymal markers and invasive capability, which can convert normal cells into tumor cells, contributing to the metastasis and invasiveness of the tumor (29). Hence, the relationship between EMT and TNBC needs to be urgently investigated.…”

“…As EMT has also been reported to be closely correlated with the survival of tumor cells (20,29), we next aimed to evaluate the effects of SMC1 overexpression on the metastasis and proliferation of TNBC cells. As a result, after SMC1 overexpression, the average number of migratory cells was 73±4.8 in hs578T and 84±4.2 in HCC1937, which was significantly higher than that of the control group (25±2.5 and 31±2.0, respectively; Fig.…”