Erythroid Differentiation Regulator 1, an Interleukin 18-Regulated Gene, Acts as a Metastasis Suppressor in Melanoma
Erythroid Differentiation Regulator 1, an Interleukin 18-Regulated Gene, Acts as a Metastasis Suppressor in Melanoma
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DOI：
10.1038/jid.2011.170
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发表时间：
2011-10-01
影响因子：
6.5
通讯作者：
Cho, Daeho
中科院分区：
文献类型：
--
作者：
Jung, Min Kyung;Park, Yoorim;Cho, Daeho
红细胞分化调节剂（Erdr1）首次在小鼠白血病细胞系中被发现，并作为应激相关存活因子发挥作用。本研究探讨了Erdr1是否调控小鼠黑色素瘤的进展，以及Erdr1调控的转移机制。Erdr1的表达与IL-18的表达呈负相关，IL-18在黑色素瘤中具有促癌作用。为了研究Erdr1作为抗癌因子的作用，我们测量了细胞的迁移、侵袭和增殖。Erdr1过表达显著抑制体外B16F10细胞的迁移、侵袭和增殖水平。此外，Erdr1过表达显著抑制黑色素瘤在体内的肺部定植、转移和肿瘤生长。为了确定与erdr1减少转移相关的因素，我们检测了热休克蛋白90 (HSP90)，这是一种众所周知的应激蛋白，也是肿瘤转移的贡献者。我们发现，在erdr1过表达的细胞中，HSP90显著降低。功能分析表明，转染HSP90小干扰RNA可降低黑色素瘤的迁移能力和转移。综上所述，Erdr1具有强大的抗转移作用，能够降低小鼠恶性黑色素瘤细胞的转移潜能。Erdr1是一种抗转移因子，可能是治疗黑色素瘤的可能治疗靶点。
Erythroid differentiation regulator (Erdr1) was first discovered in 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 an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify 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-overexpressing cells. Functional analysis demonstrated that HSP90 small-interfering RNA transfection reduced the migration ability and metastasis of melanoma. In conclusion, Erdr1 shows a powerful anti-metastasis effect that leads to the ability to reduce the metastatic potential of murine malignant melanoma cells. Erdr1 is an anti-metastatic factor that may be a possible therapeutic target for treatment of melanoma.