title: Discovery of a novel tumour metastasis-promoting gene, NVM-1.
abstract: 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.
authors: University of Heidelberg, Medical Faculty Mannheim, Germany; KIT Campus Nord, Institut für Toxikologie und Genetik, Karlsruhe, Germany. wilko.thiele@medma.uni-heidelberg.de
authors: Wilko
authors: W
authors: Thiele
authors: Natalia
authors: N
authors: Novac
authors: Sigrun
authors: S
authors: Mink
authors: Caroline
authors: C
authors: Schreiber
authors: Diana
authors: D
authors: Plaumann
authors: Johannes
authors: J
authors: Fritzmann
authors: Natascha
authors: N
authors: Cremers
authors: Melanie
authors: M
authors: Rothley
authors: Christian
authors: C
authors: Schwager
authors: Thomas
authors: T
authors: Regiert
authors: Peter E
authors: PE
authors: Huber
authors: Ulrike
authors: U
authors: Stein
authors: Peter
authors: P
authors: Schlag
authors: Jürgen
authors: J
authors: Moll
authors: Amir
authors: A
authors: Abdollahi
authors: Jonathan P
authors: JP
authors: Sleeman
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015723:Gene Library; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D008780:Methyltransferases; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
chemical_list: D009363:Neoplasm Proteins; D008780:Methyltransferases; C577899:VCPKMT protein, human