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Mol Cell Biochem (2013) 372:18 DOI 10.1007/s11010-012-1418-4
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
Jialing Zhong Mei Zhao Qing Luo
Yiming Ma Jian Liu Jia Wang Mei Yang
Xinghua Yuan Jianli Sang Changzhi Huang
Received: 10 January 2012 / Accepted: 1 August 2012 / Published online: 18 August 2012 Springer Science+Business Media, LLC. 2012
Abstract 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 signicantly reduced in gastric cancer tissues compared with normal tissues (P \ 0.001)
and lesion tissues (P \ 0.001). But no statistically signi-cant difference was observed between normal and lesion tissues (P = 0.842). In vitro transient transfection of CCDC134-specic siRNA signicantly 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 bio-marker for malignant transformation. It plays a role in regulation of cell migration and invasion, and could be a therapeutic target of gastric cancer.
Keywords CCDC134 Gastric cancer RNAi
MAPK pathway MMP-2 MMP-9
Introduction
In the last few decades, gastric cancer has shown a marked decline in incidence and mortality in many countries. However, it remains the second highest cause of cancer deaths [1]. Despite improved diagnostic and therapeutic methods, tumor invasion and metastasis are still great threats to patients [2, 3].
Mitogen-activated protein kinase (MAPK) cascades are key signaling pathways involved in regulation of cell migration and invasion, which are important factors that affect tumor progression [4, 5]. In an earlier study, increased expression of MAPK was correlated with tumorigenesis and metastatic potential for gastric cancer [6]. Hence, identifying new inhibitors that participate in the MAPK pathway should not...