Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Pigment Cell Melanoma Res. 2012 Nov;25(6):773-82. doi: 10.1111/pcmr.12005. Epub 2012 Sep 26.
Hic-5 is a shuttling protein between the cell membrane and the nucleus which functions as a focal adhesion adaptor protein and a nuclear receptor coactivator. Although several studies have shown its involvement in other types of cancer, the role of Hic-5 in melanoma is unknown. Herein, we show for the first time that Hic-5 is expressed in B16-F1 murine melanoma cells. To determine its function in melanoma cells, we used shRNA-mediated RNA interference and established stable clones with down-regulated Hic-5 expression. These clones had impaired growth and metastatic potential compared with controls in vivo, which correlated with decreased proliferation, migration and invasion in vitro. Moreover, silencing of Hic-5 expression in B16-F1 activated RhoA with an amoeboid phenotypic change, indicating that Hic-5 is a key regulator of B16-F1 metastasis in the context of Rho-dependent motility. These results provide new evidence that Hic-5 is a possible molecular target for treatment of melanoma.
Hic-5 是一种穿梭蛋白,存在于细胞膜和细胞核之间,其功能作为黏着斑衔接蛋白和核受体共激活子。虽然有几项研究表明 Hic-5 参与了其他类型的癌症,但 Hic-5 在黑色素瘤中的作用尚不清楚。在此,我们首次表明 Hic-5 在 B16-F1 鼠黑色素瘤细胞中表达。为了确定 Hic-5 在黑色素瘤细胞中的功能,我们使用 shRNA 介导的 RNA 干扰,并建立了 Hic-5 表达下调的稳定克隆。这些克隆在体内的生长和转移潜能与对照相比受损,这与体外增殖、迁移和侵袭能力下降相关。此外,B16-F1 中 Hic-5 的沉默表达激活了 RhoA,导致变形虫样表型改变,表明 Hic-5 是 Rho 依赖性运动背景下 B16-F1 转移的关键调节因子。这些结果提供了新的证据,表明 Hic-5 可能是治疗黑色素瘤的一个分子靶标。