A kelch family protein Nd1-L functions as a metastasis suppressor in cancer cells via Rho family proteins mediated mechanism
A kelch family protein Nd1-L functions as a metastasis suppressor in cancer cells via Rho family proteins mediated mechanism
复制标题
DOI：
10.3892/ijo_00000516
复制
发表时间：
2010-02-01
影响因子：
5.2
通讯作者：
Hatano, Masahiko
中科院分区：
文献类型：
--
作者：
Ohta, Yoshihito;Fujimura, Lisa;Hatano, Masahiko
BTB-kelch 蛋白 Nd1-L 作为肌动蛋白细胞骨架稳定剂，在小鼠组织中普遍表达。我们检查了 Nd1-L 对癌细胞侵袭和转移的影响。 Nd1-L 在小鼠结肠癌细胞系 Colon 26 和小鼠黑色素瘤细胞系 B16 中的过度表达导致将这些细胞接种到同种小鼠后抑制肺和肝转移，并提高动物模型的存活率。另一方面，通过RNA干扰敲低Nd1-L可促进这些细胞的转移能力。 Nd1-L 表达增加抑制癌细胞系的体外迁移和基质胶侵袭能力。因此，Nd1-L表达与癌细胞的侵袭和转移能力呈负相关。此外，NIH3T3 细胞中 Nd1-L 表达的增加抑制了生长因子诱导的 Rho 家族小 GTP 酶（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。
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.