Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing EMT in gastric cancer

Qing-Hua Cao,Yuan Lin,Man Shu,Ni Liu,Li Ding,Fang Liu,Chang-Zhao Li,Ling Xue

doi:10.1186/s12885-018-4000-y

Abstract

BackgroundTSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. However, the role of TSP50 in gastric cancer remains elusive.MethodsqRT-PCR, western blot were used to determine TSP50 expression in gastric cancer cell lines. Role of TSP50 in proliferation and invasion was examined by BrdU incorporation assay, cell count, wound healing and transwell assay. Immunohistochemistry and western blot were performed to identify the potential mechanisms involved.ResultsTSP50 was highly expressed in most of the gastric cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in gastric cancer cells enhanced proliferation and invasiveness, whereas down-regulation of TSP50 by its specific shRNA decreased it. A negative correlation between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination of them improves the prediction for prognosis and lymph node metastasis. Mechanistic studies revealed that overexpression of TSP50 increased the expression of epithelial-to-mesenchymal transition (EMT) markers including Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-κB signaling pathway is involved in the regulatory effects of TSP50 on EMT, migration and invasion in gastric cancer cells.ConclusionTSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-κB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer.

Highlights

Testes-specific protease 50 (TSP50) has been reported to be a candidate oncogene and is overexpressed in various cancers
Quantitative polymerase chain reaction (PCR) and western blot analysis revealed that the level of TSP50 expression was higher in almost all gastric cancer cell lines, except MGC-803, when compared to GES-1 cell at both the mRNA and protein levels (Fig. 1a, b)
Overexpression of TSP50 promotes proliferation, migration and invasion of MGC-803 cell In our previous study, TSP50 expression positively correlated with lymph node metastasis status and later disease stage [11]

Summary

Introduction

TSP50 (testes-specific protease 50) has been reported to be a candidate oncogene and is overexpressed in various cancers. Our previous study demonstrated that TSP50 protein is elevated in gastric cancer, and its high expression is associated with unfavorable prognosis and lymph node metastasis. The role of TSP50 in gastric cancer remains elusive. It is imperative to explore the underlying mechanism of gastric cancer metastasis in order to Testes-specific protease 50 (TSP50) is a novel member of cancer/testis antigens (CTAs), which is not expressed in normal tissues except testes and cancers, including breast cancer, colorectal cancer, laryngocarcinoma and cervical cancer [5,6,7,8,9,10]. We recently reported that TSP50 expression was up-regulated in gastric cancer tissues compared with adjacent non-tumor mucosa. TSP50 overexpression was associated with lymph node metastasis and poor prognosis in gastric cancer patients [11]. Cao et al BMC Cancer (2018) 18:94 the biologic role and molecular mechanisms of TSP50 in gastric cancer metastasis remain to be elucidated

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