CCDC134 is down-regulated in gastric cancer and its silencing promotes cell migration and invasion of GES-1 and AGS cells via the MAPK pathway
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CCDC134 (coiled coil domain containing 134), a novel secretory protein, acts as an inhibitor of Erk1/2 and JNK/SAPK pathways. However, the role of CCDC134 in cancer development is still lacking. In this study, we found that CCDC134 expression significantly reduced in gastric cancer tissues compared with normal tissues (P < 0.001) and lesion tissues (P < 0.001). But no statistically significant difference was observed between normal and lesion tissues (P = 0.842). In vitro transient transfection of CCDC134-specific siRNA significantly promoted the migration and invasion of both the normal gastric epithelial cell line GES-1 and gastric cancer cell line AGS cells. Further analysis revealed that the attenuated expression of CCDC134 promoted the activation of Erk1/2 and JNK/SAPK, but had no effect on p38. The activation of Erk1/2 and JNK/SAPK was required for CCDC134-mediated migration and invasion. Besides, CCDC134-RNAi could induce the expression of MMP-2 and MMP-9, which are key molecules involved in regulating cell migration and invasion. Therefore, CCDC134 may be a candidate biomarker for malignant transformation. It plays a role in regulation of cell migration and invasion, and could be a therapeutic target of gastric cancer.
KeywordsCCDC134 Gastric cancer RNAi MAPK pathway MMP-2 MMP-9
This study was supported by the National Key Basic Research Program of China (2007CB914700) and Open projects (201102) of Key Laboratory of Cell Proliferation and Regulation Biology (Beijing Normal University), Ministry of Education. We are grateful to Professor Xiaoyan Qiu (Peking University, Beijing, P.R. China) for providing us with antibody of CCDC134.
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