Recombinant Erdr1 suppresses the migration and invasion ability of human gastric cancer cells, SNU-216, through the JNK pathway

Abstract

Erythroid differentiation regulator 1 (Erdr1) suppressed cell motility in vitro and has anti-metastatic effect in vivo on melanoma. The current study investigated the effect of recombinant Erdr1 on the migration and invasion ability of SNU-216 cell, a gastric cancer cell line. The expression of Erdr1 is inversely correlated with IL-18 expression, which has a pro-cancer effect in gastric cancer. Treatment with rErdr1 markedly suppressed the ability of SNU-216 cells to migrate and invade, indicating that recombinant Erdr1 inhibited the motility of gastric cancer cells. E-cadherin expression levels were measured to determine the factor involved in the rErdr1-suppressed motility. E-cadherin is a representative of the cadherin family, known as cell motility enhancement adhesion molecule. Our results revealed that E-cadherin levels were increased by rErdr1 treatment, suggesting the involvement of E-cadherin in rErdr1-reduced cell migration. The cells were treated with specific MAPK inhibitors such as SP600125, SB203580 or PD98059 to identify the signaling mechanism involved with rErdr1 suppressed cell migration. The results indicated that the rErdr1 inhibited migration was primarily reversed by SP600125, a JNK inhibitor. In addition, the level of JNK phosphorylation was markedly increased by recombinant Erdr1. Taken together, these findings suggest that rErdr1 suppressed the ability of gastric cancer cells to metastasis by up regulating E-cadherin through a JNK pathway activation. Furthermore, it can be suggested that the inhibitory effect of recombinant Erdr1 on SNU-216 cell's metastatic potential was through cell motility suppression.