GBP5 通过 Src/ERK1/2/MMP3 通路驱动脑胶质母细胞瘤的恶性转化。

GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway.

机构信息

Central Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

出版信息

Cell Death Dis. 2021 Feb 19;12(2):203. doi: 10.1038/s41419-021-03492-3.

Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

鸟苷酸结合蛋白（GBPs）是干扰素诱导的大型 GTPase 家族，在细胞自主免疫和肿瘤恶性转化中发挥关键作用。胶质母细胞瘤（GBM）是成人中最常见和最致命的原发性脑肿瘤。在这里，我们发现 GBP5 在 GBM 细胞系和临床样本中高度表达，特别是在间充质亚型中。GBP5 的表达水平与 GBM 患者的预后呈负相关。GBP5 的过表达促进了 GBM 细胞在体外和体内的增殖、迁移和侵袭。相比之下，通过 RNA 干扰沉默 GBP5 则表现出相反的效果。因此，在 GBM 细胞中靶向 GBP5 导致肿瘤生长受损和携带 GBM 肿瘤的小鼠存活时间延长。我们进一步确定 Src/ERK1/2/MMP3 轴对于 GBP5 促进 GBM 侵袭至关重要。这些发现表明，GBP5 可能成为 GBM 干预的新靶标。