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.
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.
Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People's Republic of China.
Jialing
J
Zhong
Mei
M
Zhao
Qing
Q
Luo
Yiming
Y
Ma
Jian
J
Liu
Jia
J
Wang
Mei
M
Yang
Xinghua
X
Yuan
Jianli
J
Sang
Changzhi
C
Huang
D002460:Cell Line; D002465:Cell Movement; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C576232:CCDC134 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9