Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chuo-ku, Chiba city, Chiba 260-8670, Japan.
Int J Oncol. 2010 Feb;36(2):427-34.
The BTB-kelch protein Nd1-L acts as an actin cytoskeleton stabilizer expressed ubiquitously in mouse tissues. We examined the effect of Nd1-L on cancer cell invasion and metastasis. Over-expression of Nd1-L in murine colon carcinoma cell line Colon 26 and murine melanoma cell line B16 resulted in suppression of pulmonary and liver metastasis after inoculation of these cells to syngeneric mice and in increased survival in an animal model. On the other hand, knock down of Nd1-L by RNA interference promoted metastasis ability of these cells. Increased expression of Nd1-L inhibited migration and Matrigel invasion capacity of cancer cell lines in vitro. Thus, Nd1-L expression inversely correlated with invasive and metastasis capacity of cancer cells. Furthermore, increased expression of Nd1-L in NIH3T3 cells inhibited growth factor induced activation of Rho family small GTPases such as Rho, Rac and cdc42. These results suggest that Nd1-L is involved in invasion and metastasis of cancer cells by regulating the actin cytoskeleton and Rho family proteins.
BTB-kelch 蛋白 Nd1-L 作为一种肌动蛋白细胞骨架稳定剂，在小鼠组织中广泛表达。我们研究了 Nd1-L 对癌细胞侵袭和转移的影响。Nd1-L 在鼠结肠癌细胞系 Colon 26 和鼠黑色素瘤细胞系 B16 中的过表达导致这些细胞接种到同基因小鼠后肺和肝转移的抑制，并在动物模型中提高了存活率。另一方面，RNA 干扰下调 Nd1-L 促进了这些细胞的转移能力。Nd1-L 的高表达抑制了体外癌细胞系的迁移和 Matrigel 侵袭能力。因此，Nd1-L 的表达与癌细胞的侵袭和转移能力呈负相关。此外，Nd1-L 在 NIH3T3 细胞中的高表达抑制了生长因子诱导的 Rho 家族小 GTPases（如 Rho、Rac 和 cdc42）的激活。这些结果表明，Nd1-L 通过调节肌动蛋白细胞骨架和 Rho 家族蛋白参与癌细胞的侵袭和转移。
