CAGE, a novel cancer/testis antigen gene, promotes cell motility by activation ERK and p38 MAPK and downregulating ROS.
We previously identified a novel cancer/testis antigen gene CAGE by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera of gastric cancer patients. CAGE is expressed in many cancers and cancer cell lines, but not in normal tissues apart from the testis. In the present study, we investigated its role in the motility of cells of two human cancer cell lines: HeLa and the human hepatic cancer cell line, SNU387. Induction of CAGE by tetracycline or transient transfection enhanced the migration and invasiveness of HeLa cells, but not the adhesiveness of either cell line. Overexpression of CAGE led to activation of ERK and p38 MAPK but not Akt, and inhibition of ERK by PD98059 or p38 MAPK by SB203580 counteracted the CAGE-promoted increase in motility in both cell lines. Overexpression of CAGE also resulted in a reduction of ROS and an increase of ROS scavenging, associated with induction of catalase activity. Inhibition of ERK and p38 MAPK increased ROS levels in cells transfected with CAGE, suggesting that ROS reduce the motility of both cell lines. Inhibition of ERK and p38 MAPK reduced the induction of catalase activity resulting from overexpression of CAGE, and inhibition of catalase reduced CAGE-promoted motility. We conclude that CAGE enhances the motility of cancer cells by activating ERK and p38 MAPK, inducing catalase activity, and reducing ROS levels.
Shim
Hyeeun
H
School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Shim
Eunsook
E
Lee
Hansoo
H
Hahn
Janghee
J
Kang
Dongmin
D
Lee
Yun-Sil
YS
Jeoung
Dooil
D
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D034961:Antigens, Nuclear / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D002374:Catalase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C454199:DDX53 protein, human; D053487:DEAD-box RNA Helicases