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.