title: Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
abstract: Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we sequenced the entire coding region of EPHB6 in 80 non-small cell lung cancer patients and 3 tumor cell lines. Three potentially relevant mutations were identified in primary patient samples of NSCLC patients (3.8%). Two point mutations led to instable proteins. An in frame deletion mutation (del915-917) showed enhanced migration and accelerated wound healing in vitro. Furthermore, the del915-917 mutation increased the metastatic capability of NSCLC cells in an in vivo mouse model. Our results suggest that EPHB6 mutations promote metastasis in a subset of patients with non-small cell lung cancer.
authors.affiliation: Department of Medicine A - Hematology, Oncology, Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Etmar
authors.initials: E
authors.lastname: Bulk
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Antje
authors.initials: A
authors.lastname: Hascher
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Rainer
authors.initials: R
authors.lastname: Wiewrodt
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.forename: Bernd
authors.initials: B
authors.lastname: Timmermann
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marra
authors.forename: Ludger
authors.initials: L
authors.lastname: Hillejan
authors.forename: Karsten
authors.initials: K
authors.lastname: Wiebe
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schwab
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D060888:Real-Time Polymerase Chain Reaction; D036261:Receptor, EphB6 / Q000235:genetics*
chemical_list: D017931:DNA Primers; D036261:Receptor, EphB6