α-辅肌动蛋白 1 和 α-辅肌动蛋白 4：在星形细胞瘤细胞存活、迁移和 RhoA 信号中的作用相反。

Alpha-actinin 1 and alpha-actinin 4: contrasting roles in the survival, motility, and RhoA signaling of astrocytoma cells.

机构信息

Department of Biology, Grambling State University, Grambling, LA 71245, USA.

出版信息

Exp Cell Res. 2010 Apr 15;316(7):1137-47. doi: 10.1016/j.yexcr.2010.02.011. Epub 2010 Feb 12.

DOI:10.1016/j.yexcr.2010.02.011

PMID:20156433

Abstract

Alpha-actinin is a prominent actin filament associated protein for which different isoforms exist. Here, we have examined whether the two highly homologous non-muscle alpha-actinin isoforms 1 and 4 exhibit functional differences in astrocytoma cells. The protein levels of these isoforms were differentially regulated during the development and progression of astrocytomas, as alpha-actinin 1 was higher in astrocytomas compared to normal brains whereas alpha-actinin 4 was elevated in high-grade astrocytomas compared to normal brains and low grade astrocytomas. RNAi demonstrated contrasted contributions of alpha-actinin 1 and 4 to the malignant behavior of U-373, U-87 and A172 astrocytoma cells. While alpha-actinin 1 appeared to favor the expansion of U-373, U-87 and A172 astrocytoma cell populations, alpha-actinin 4 played this role only for U-373 cells. On the other hand, downregulation of alpha-actinin 4, but not 1, reduced cell motility, adhesion, cortical actin, and RhoA levels. Finally, in the three astrocytoma cell lines examined, alpha-actinin 1 and 4 had contrasted biochemical properties as alpha-actinin 4 was significantly more abundant in the actin cytoskeleton than alpha-actinin 1. Collectively, these findings suggest that alpha-actinin 1 and 4 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells.

摘要

α-辅肌动蛋白是一种重要的肌动蛋白丝相关蛋白，存在不同的亚型。在这里，我们研究了两种高度同源的非肌肉α-辅肌动蛋白亚型 1 和 4 在星形细胞瘤细胞中是否表现出功能差异。这些亚型的蛋白水平在星形细胞瘤的发生和发展过程中存在差异调节，α-辅肌动蛋白 1 在星形细胞瘤中的水平高于正常脑组织，而α-辅肌动蛋白 4 在高级别星形细胞瘤中的水平高于正常脑组织和低级别星形细胞瘤。RNAi 实验表明，α-辅肌动蛋白 1 和 4 对 U-373、U-87 和 A172 星形细胞瘤细胞的恶性行为有不同的作用。虽然 α-辅肌动蛋白 1 似乎有利于 U-373、U-87 和 A172 星形细胞瘤细胞群体的扩增，但α-辅肌动蛋白 4 仅对 U-373 细胞起作用。另一方面，下调α-辅肌动蛋白 4，但不是α-辅肌动蛋白 1，会降低细胞迁移、黏附、皮质肌动蛋白和 RhoA 水平。最后，在研究的三种星形细胞瘤细胞系中，α-辅肌动蛋白 1 和 4 具有不同的生化特性，因为α-辅肌动蛋白 4 在肌动蛋白细胞骨架中的含量明显高于α-辅肌动蛋白 1。总之，这些发现表明，α-辅肌动蛋白 1 和 4 在星形细胞瘤的发生和发展过程中存在差异调节，因为这两种亚型都独特地有助于星形细胞瘤细胞的不同恶性特征。