State Key Laboratory of Virology, College of Life Sciences, Wuhan University, and Department of Urology, Tongji Hospital, Hubei, Wuhan, PR China.
Oncol Rep. 2013 Jan;29(1):109-16. doi: 10.3892/or.2012.2069. Epub 2012 Oct 4.
Cervical cancer is a common malignancy in women worldwide, and the occurrence of invasion and metastasis is the major cause for most cancer-related deaths. Epithelial-mesenchymal transition (EMT) has been implicated in the metastasis of primary tumors and provides molecular mechanisms for cervical cancer metastasis. We previously reported that Nogo-B mediates cell motility by binding Fibulin-5. Herein, we show that the increased expression of Nogo-B is correlated with the degree of cervical cancer metastasis. In HeLa cervical cancer cells, overexpression of Nogo-B induces the EMT and promotes cell migration and invasion, while inhibiting cell adhesion. Furthermore, we found that Nogo-B accumulates and co-localizes with Fibulin-5 in pseudopods, and the downstream effects of overexpression of Nogo-B on cell motility could be partially abolished by RNA interference against Fibulin-5. These results suggest that Nogo-B functions as an inducer of cervical cancer metastasis and that this effect is mediated, at least in part, through Fibulin-5.
宫颈癌是全球女性中常见的恶性肿瘤，侵袭和转移的发生是大多数癌症相关死亡的主要原因。上皮-间充质转化（EMT）已被涉及到原发性肿瘤的转移，并为宫颈癌转移提供了分子机制。我们之前报道过 Nogo-B 通过与 Fibulin-5 结合来介导细胞迁移。在此，我们表明 Nogo-B 的表达增加与宫颈癌转移的程度相关。在 HeLa 宫颈癌细胞中，Nogo-B 的过表达诱导 EMT 并促进细胞迁移和侵袭，同时抑制细胞黏附。此外，我们发现 Nogo-B 在伪足中积累并与 Fibulin-5 共定位，并且针对 Fibulin-5 的 RNA 干扰可以部分消除 Nogo-B 过表达对细胞迁移的下游影响。这些结果表明 Nogo-B 作为宫颈癌转移的诱导因子发挥作用，并且这种作用至少部分通过 Fibulin-5 介导。
