Interleukin 18 regulated gene, erythroid differentiation regulator 1 acts as metastasis suppressor in murine melanoma. (127.5)

Abstract

Abstract Erythroid differentiation regulator (Erdr1) was first discovered on mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression which has a pro-cancer effect in melanoma. To study the role of Erdr1 as anti-cancer factor, cell migration and invasion ability were measured. Erdr1 over-expression markedly inhibited the level of cell migration and invasion ability in B16F10 cells, in vitro. Additionally, Erdr1 over-expression significantly suppressed melanoma lung colonization and metastasis, in vivo. In order to indentify the factors involved in Erdr1-reduced metastasis, heat shock protein 90 (HSP90), a well known stress protein and contributor to tumor metastasis, was examined. We found that HSP90 was significantly decreased in Erdr1 over-expressing cells. Functional analysis demonstrated that HSP90 siRNA transfection reduced the migration ability and metastasis of melanoma. In conclusion, Erdr1 shows powerful anti-metastasis effect that leads to ability to reduce the metastatic potential of murine malignant melanoma cells. Erdr1 is a novel anti-metastatic factor and may be a possible therapeutic target for treatment of melanoma.