Abstract
BackgroundGlobally, the incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis. Therefore, the molecular mechanisms associated with the migration and invasion of gastric cancer cells are important for gastric cancer treatment. Previously, TSPAN9 has been reported to inhibit gastric cancer cell migration; however, the underlying molecular mechanism remains unclear.MethodsHuman gastric adenocarcinoma cell lines, SGC7901 and AGS, were cultured in vitro. TSPAN9 expression was determined by RT-PCR, western blot analysis, and immunohistochemistry in gastric cancer and tumor-adjacent tissues. Following the over-expression and knockdown of TSPAN9, wound healing and cell invasion assays were performed and EMT-related protein expression was evaluated to analyze the invasion and migration of gastric cancer cells. TSPAN9 expression and the invasion and metastasis of gastric cancer cells were observed by the functional assays following EMILIN1 over-expression.ResultsInhibiting TSPAN9 expression significantly promoted the migration and invasion of gastric cancer cells. In addition, immunofluorescence co-localization and co-immunoprecipitation analysis revealed closely related expression of EMILIN1 and TSPAN9. Moreover, EMILIN1 can synergistically boost the tumor suppressive effect of TSPAN9, which may be produced by promoting TSPAN9 expression.ConclusionsWe have demonstrated that EMILIN1 induces anti-tumor effects by up-regulating TSPAN9 expression in gastric cancer. Hence, membrane proteins TSPAN9 and EMILIN1 may represent novel therapeutic targets for the treatment of gastric cancer.
Highlights
The incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis
We found that TSPAN9 can disrupt gastric cancer cell invasion and migration, and EMILIN1 can synergistically promote the anti-cancer effects of TSPAN9
Gastric cancer cell TSPAN9 expression Members of the TSPAN family have been shown to be overexpressed in some tumor cells [5], but currently there is no report on TSPAN9 expression in gastric cancer
Summary
The incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis. The molecular mechanisms associated with the migration and invasion of gastric cancer cells are important for gastric cancer treatment. TSPAN9 has been reported to inhibit gastric cancer cell migration; the underlying molecular mechanism remains unclear. It is important that the molecular mechanisms governing gastric cancer’s development and progression be elucidated in order to better facilitate active early screening. 33 TSPAN proteins have been found in humans, including CD9, CD63, CD151, TSPAN1 and TSPAN8 [5]. These proteins have been shown to be involved in cell development, differentiation, movement, as well as in tumor proliferation and invasion [6, 7].
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