Discovery of a novel tumour metastasis-promoting gene, NVM-1

• Published in: The Journal of pathology 2011-09, Vol.225 (1), p.96-105
• Main Authors: Thiele, Wilko, Novac, Natalia, Mink, Sigrun, Schreiber, Caroline, Plaumann, Diana, Fritzmann, Johannes, Cremers, Natascha, Rothley, Melanie, Schwager, Christian, Regiert, Thomas, Huber, Peter E., Stein, Ulrike, Schlag, Peter, Moll, Jürgen, Abdollahi, Amir, Sleeman, Jonathan P.
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Animals; Biological and medical sciences; Cell migration; chromosome 14; Chromosomes, Human, Pair 14 - genetics; dissemination; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Library; Genes, Neoplasm; Humans; invasion; Investigative techniques, diagnostic techniques (general aspects); Major histocompatibility complex; Male; Medical sciences; Metastases; metastasis; Mice; Mice, SCID; motility; Neoplasm Invasiveness; Neoplasm Metastasis - genetics; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Transplantation; Neoplasms - metabolism; Neoplasms - pathology; Overexpression; Pancreatic carcinoma; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phenotype; Tissue inhibitor of metalloproteinase 4; Transcription; tumour
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2924

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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.