Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea.
FEBS Lett. 2011 Jul 21;585(14):2331-8. doi: 10.1016/j.febslet.2011.05.070. Epub 2011 Jun 23.
A subpopulation of cancer cells with stem cell properties is responsible for tumor formation, maintenance, and malignant progression; however, the molecular mechanisms underlying the maintenance of cancer stem-like cell properties have remained unclear. Here, we show that the Rho family GTPase Rac1 is involved in the glioma stem-like cell (GSLC) maintenance and tumorigenicity in human glioma. The Rac1-Pak signaling was markedly activated in GSLCs. Knockdown of Rac1 caused reduction of expression of GSLC markers, self-renewal-related proteins and neurosphere formation. Moreover, down-regulation of Rac1 suppressed the migration, invasion, and malignant transformation in GSLCs. Furthermore, inhibition of Rac1 enhanced radiation sensitivity of GSLCs. These results indicate that the small GTPase Rac1 is involved in the maintenance of stemness and malignancies in GSLCs.
具有干细胞特性的癌细胞亚群负责肿瘤的形成、维持和恶性进展；然而，维持癌症干细胞样细胞特性的分子机制仍不清楚。在这里，我们表明 Rho 家族 GTP 酶 Rac1 参与了人神经胶质瘤中的神经胶质瘤干细胞样细胞（GSLC）的维持和致瘤性。Rac1-Pak 信号在 GSLC 中明显被激活。Rac1 的敲低导致 GSLC 标志物、自我更新相关蛋白和神经球形成的表达减少。此外，下调 Rac1 抑制了 GSLC 的迁移、侵袭和恶性转化。此外，抑制 Rac1 增强了 GSLC 的辐射敏感性。这些结果表明，小分子 GTP 酶 Rac1 参与了 GSLC 干性和恶性的维持。
