University of Heidelberg, Medical Faculty Mannheim, Germany; KIT Campus Nord, Institut für Toxikologie und Genetik, Karlsruhe, Germany.
J Pathol. 2011 Sep;225(1):96-105. doi: 10.1002/path.2924. Epub 2011 Jul 8.
We have previously reported that over-expression of a panel of 119 genes correlates with the metastatic potential of pancreatic carcinoma cells. We sought to identify and functionally characterize candidate tumour metastasis promoting genes among this library using a secondary phenotype-assisted screen. Here we report the discovery of the metastasis-promoting function of a hitherto not characterized gene located on chromosome 14 (ORF138), which we have named 'novel metastasis-promoting gene 1' (NVM-1). The NVM-1 transcript is extensively alternatively spliced, is expressed endogenously in a number of different tissues, and is strongly over-expressed at the protein level in a variety of human tumour types. Importantly, NVM-1 expression stimulates the migratory and invasive behaviour of tumour cells and promotes metastasis formation in experimental animals in vivo. Up-regulation of FMNL2 and MT1E and down-regulation of TIMP4 and MHC-I is observed as a consequence of NVM-1 expression. Together these data identify NVM-1 as a gene that is functionally involved in tumour metastasis, and suggest that NVM-1 may constitute a promising therapeutic target for inhibition of tumour metastasis.
我们之前曾报道过，一组 119 个基因的过表达与胰腺癌细胞的转移潜能相关。我们试图在这个文库中通过辅助二次表型筛选来鉴定和功能表征候选肿瘤转移促进基因。在这里，我们报告了一种位于 14 号染色体（ORF138）上的、迄今尚未被描述的基因（命名为“新型转移促进基因 1”（NVM-1））的转移促进功能的发现。NVM-1 转录物广泛地进行选择性剪接，在许多不同的组织中内源性表达，并且在各种人类肿瘤类型中在蛋白质水平上强烈过表达。重要的是，NVM-1 表达刺激肿瘤细胞的迁移和侵袭行为，并在体内实验动物中促进转移形成。NVM-1 表达导致 FMNL2 和 MT1E 的上调以及 TIMP4 和 MHC-I 的下调。这些数据共同表明 NVM-1 是一种在肿瘤转移中具有功能的基因，并表明 NVM-1 可能成为抑制肿瘤转移的有前途的治疗靶点。
