TES was epigenetically silenced and suppressed the epithelial–mesenchymal transition in breast cancer

Abstract

The TES gene was frequently lost in breast cancer, which could inhibit tumor invasion and the formation of distant metastasis. However, the underlying mechanisms remain unknown yet. In the present study, we aimed to investigate how TES was silenced and its roles in EMT--the key step for tumor metastasis. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the mRNA and protein expression of target genes; the status of TES promoter was determined by methylation-specific PCR and subsequently, DNA sequencing. Overexpression or downregulation of TES was achieved by pcDNA3.1-TES or shRNA-TES transfection. Cellular adhesion and migration were investigated by the adhesion and Transwell assays. Morphological changes of breast cancer cells were observed under the optical microscope. The Rho A activity was measured using a commercial kit, and its roles in TES-manipulated EMT were determined by real-time PCR and Western blot. The 42.3% (33/78) breast cancer tissues presented hypermethylation of the TES gene, whereas only 2 (2.6%) non-malignant cases were hypermethylated (P<0.001). Moreover, TES hypermethylation was significantly correlated with larger tumor diameter (P=0.03) and lympho node metastasis (P=0.024). In primary cultured breast cancer cells, the demethylation treatment using 5-aza-dC notably restored the expression of TES. In vitro, overexpression of TES enhanced cellular adhesion inhibited migration and suppressed EMT, while downregulation of TES impaired cellular adhesion, promoted migration, and enhanced EMT. TES overexpression also activated the Rho A signal, which is a critical factor for the effects of TES on the EMT procedure. We firstly proved that frequent loss of TES in breast cancer was caused by promoter hypermethylation, which was correlated with poor prognosis. In vitro, TES enhanced cellular adhesion, suppressed tumor migration, and inhibited EMT. Moreover, the Rho A pathway was critical for the effects of TES on EMT, which can be blocked by the Rho A inhibitor. Therefore, we propose restoration of TES as a potent strategy for breast cancer therapy.

Mutation profiling in eight cases of vagal paragangliomas

“…This gene is involved in tumor cell growth and metastasis [ 91 ]. In this patient’s VPGL, we also observed a variant NM_015641: c.G1123A, p.V375M (chr7: 115897393, rs202205760) in TES , a tumor suppressor gene involved in the regulation of tumorigenesis, angiogenesis, and metastasis [ 92 ]. Additionally, a likely pathogenic variant NM_017672: c.C1337G, p.A446G (chr15: 50916466) in the TRPM7 gene was found.…”

Reduced RBPMS Levels Promote Cell Proliferation and Decrease Cisplatin Sensitivity in Ovarian Cancer Cells

“…The upregulation of FOXL2 (downregulated upon RBPMS knockout) has been found to suppress cervical cancer cell proliferation and facilitate the apoptosis of these cells [ 69 , 70 ]; thus, it could be important to study the role of FOXL2 in ovarian cancer. Furthermore, the deregulation of other downregulated genes following RBPMS knockout, including PDGFD, TES, CARD16, and KNF521, has been linked to the progression of many cancer types [ 71 , 72 , 73 ], and the role of these genes in the ovarian cancer setting should be investigated.…”

TES functions as a Mena‐dependent tumor suppressor in gastric cancer carcinogenesis and metastasis

“…TES functions as a necessary tumor suppressor of colorectal cancer progression by activating mitogen-activated protein kinase (p38-MAPK) signaling pathways [27]. TES suppressed the epithelial-mesenchymal transition in endometrial cancer [28] and breast cancer [29]. Other investigators have reported that TES binds to the EVH1 domain of Mena with its LIM3 domain [5].…”