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

Abstract

Abstract. Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which is characterized by the negative form of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). TNBC accounts for ~15% of all breast cancer forms, and often leads to high mortality and poor prognosis. Structural maintenance of chromosome 1 (SMC1) is a subunit of the cohesion protein complex. Brachyury is a protein that is encoded by the T gene in humans, which is a transcription factor within the T-box complex of genes. Epithelial-mesenchymal transition (EMT) is a ubiquitous process in the body, and in particular, induces metastasis and the proliferation of cancer cells. In the present study, we found that SMC1 expression in TNBC tissues exceeded its expression in adjacent non-tumor tissues. Similarly, the expression of SMC1 in TNBC cell lines (hs578T and HCC1937) was found to be higher than in MCF10a and MCF7 cells. Subsequently, SMC1 was overexpressed and silenced in hs578T and HCC1937 cells through plasmid and siRNA transfection, respectively. The results showed that the high expression of SMC1 often promoted EMT, accompanied by the enhanced expression of Brachyury. Besides, upregulated expression of Brachyury through plasmid transfection also significantly improved the level of EMT, which further indicated that SMC1 increased EMT in TNBC through the induction of Brachyury expression. Taken together, these results contributed to a better understanding of the pathogenesis of TNBC, which also provided an experimental basis for the prevention, diagnosis and treatment of TNBC.

Machine Learning based Tissue Analysis Reveals Brachyury has a Diagnosis Value in Breast Cancer

“…Therefore, EMT makes tumor cells more invasive and resistant. Although in previous study, we have found that Brachyury can promote the occurrence of EMT of breast cancer cells [4,5], there is no clinical data supporting this. In this study, we prepared para n tissue from 303 cases of breast cancer tissues, constructed tissue chips, and tried to evaluate the value of Brachyury protein expression in breast cancer prognostic analysis using machine learning algorithms.…”

The Roles of Embryonic Transcription Factor BRACHYURY in Tumorigenesis and Progression

“…BRACHYURY/BRACHYURY is obviously highly expressed at the mRNA and protein levels in breast cancer tissues and cell lines compared to negativity in normal breast cancer tissues and cells (9,60,(63)(64)(65)(66). Hormone receptor status of breast cancer is an important and recognized prognostic factor and can reflect different stages (67), including estrogen receptor (ER) and progesterone receptor (PR).…”

Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer

“…Post-developmentally, brachyury is expressed in the testes and some thyroid tissues, but is undetectable in all other non-neoplastic adult tissues (Edwards et al, 1996; Hamilton et al, 2015). Interestingly, recent studies have reported the expression of brachyury in several epithelial cancers where it promotes growth, confers resistance to chemo- and radiotherapy, and drives epithelial-to-mesenchymal transition (EMT) (Cho et al, 2010; Fernando et al, 2010; Haro et al, 2013; Huang et al, 2013; Imajyo et al, 2012; Jezkova et al, 2016; Kobayashi et al, 2014; Larocca et al, 2013; Li et al, 2016; Miettinen et al, 2015; Palena et al, 2014; Park et al, 2008; Pinto et al, 2015; Pinto et al, 2014; Pires and Aaronson, 2014; Roselli et al, 2012; Sarkar et al, 2012; Shao et al, 2015; Shimoda et al, 2012; Vujovic et al, 2006; Xu et al, 2015; Yoshihama et al, 2016); however, the mechanistic details of how brachyury mediates these features of tumor progression have not been fully elucidated. Furthermore, the lack of brachyury expression in most adult non-neoplastic tissues and exclusive tumor-specific expression underscores its value as a potential diagnostic and therapeutic target in cancer.…”