Hepatocellular carcinoma (HCC) is ranked as the fifth most frequent cancer and third most frequent cause of cancer deaths in the world [
1]. In spite of improvements in surveillance and clinical therapeutic strategy, long-term disease-free survival (DFS) of patients with HCC remains unsatisfactory due to tumor recurrence and metastasis of the primary tumor [
2],[
3]. Metastasis is not only a complex process but also the major cause of cancer-related deaths [
4]. Epithelial-mesenchymal transition (EMT) describes a series of events during which cells lose epithelial characteristics such as cell-layer organization and apical-basolateral polarization and acquire properties of mesenchymal or fibroblastoid cells including motility [
5]. EMT is known to be a central mechanism responsible for invasiveness and metastasis of various cancers [
6],[
7]. Increasing evidences suggest that activation of Rho-family of small GTPases, cytoskeletal rearrangement, and nuclear translocation of several transcription factors such as Snail and Twist play important roles in the processes of cancer cell metastasis through modulation of cancer cells EMT [
8]-[
10]. However, the underlying mechanisms of cancer-related EMT are not fully elucidated.
The T-box transcription factor, Brachyury, is vital for the formation and differentiation of posterior mesoderm and axial development in vertebrates [
11]. Interestingly, Brachyury is located at 6q27, which is a frequently amplified region in HCC [
12]. The function of Brachyury has extensively been characterized in mice and zebrafish [
13],[
14]. An earlier study on Brachyury-mutant mice model without T protein reported in utero death with abnormal notochord, absent somites, and reduced allantois [
15]. In zebrafish, the no-tail mutation (Ntl) is the homolog of Brachyury; the Ntl embryos die soon after hatching with lack notochords and tails, and they possess abnormal trunk somites. The T gene encodes a transcription factor that binds to a specific DNA element via its N-terminal region [
14]. In humans, T-box transcription factors are major players in the regulation of the progenitors and their differentiated descendants [
11],[
16]. Brachyury is expressed in the progenitor population throughout somitogenesis, suggesting that it plays an essential role in keeping the progenitor population viable [
17]. Meanwhile, Brachyury is also dysregulated in various human malignant neoplasms [
18],[
19]. Recently, Brachyury was demonstrated to induce EMT in human epithelial cells through induction Snail, Slug, and downstream signal [
20]. An earlier study on human lung carcinoma cells (in vitro and in vivo) has demonstrated that overexpressed Brachyury divides at slower rates than those with low-expressed Brachyury, a phenomenon associated with marked downregulation of cyclin D1, phosphorylated Rb, and CDKN1A (p21) [
21]. Another study on oral squamous cell carcinoma cells demonstrated that the expression of Brachyury was correlated with EMT and was significantly associated with lymph node and distant metastasis [
22]. The above evidences indicate that Brachyury may be a critical regulator of carcinogenesis and tumor metastases in different cancers. Until now, no studies have reported its roles in HCC. Hence, the present study aimed to evaluate the Brachyury expression in patients with HCC and in HCC cell lines and its clinicopathological significance in HCC.