Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.

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...

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Main Authors: Etmar Bulk, Jun Yu, Antje Hascher, Steffen Koschmieder, Rainer Wiewrodt, Utz Krug, Bernd Timmermann, Alessandro Marra, Ludger Hillejan, Karsten Wiebe, Wolfgang E Berdel, Albrecht Schwab, Carsten Müller-Tidow
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3514309?pdf=render
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author Etmar Bulk
Jun Yu
Antje Hascher
Steffen Koschmieder
Rainer Wiewrodt
Utz Krug
Bernd Timmermann
Alessandro Marra
Ludger Hillejan
Karsten Wiebe
Wolfgang E Berdel
Albrecht Schwab
Carsten Müller-Tidow
author_facet Etmar Bulk
Jun Yu
Antje Hascher
Steffen Koschmieder
Rainer Wiewrodt
Utz Krug
Bernd Timmermann
Alessandro Marra
Ludger Hillejan
Karsten Wiebe
Wolfgang E Berdel
Albrecht Schwab
Carsten Müller-Tidow
author_sort Etmar Bulk
collection DOAJ
description 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.
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spelling doaj.art-555361feb8b7495f946ef0e5f27071ac2022-12-22T03:16:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e4459110.1371/journal.pone.0044591Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.Etmar BulkJun YuAntje HascherSteffen KoschmiederRainer WiewrodtUtz KrugBernd TimmermannAlessandro MarraLudger HillejanKarsten WiebeWolfgang E BerdelAlbrecht SchwabCarsten Müller-TidowAlterations 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.http://europepmc.org/articles/PMC3514309?pdf=render
spellingShingle Etmar Bulk
Jun Yu
Antje Hascher
Steffen Koschmieder
Rainer Wiewrodt
Utz Krug
Bernd Timmermann
Alessandro Marra
Ludger Hillejan
Karsten Wiebe
Wolfgang E Berdel
Albrecht Schwab
Carsten Müller-Tidow
Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
PLoS ONE
title Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
title_full Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
title_fullStr Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
title_full_unstemmed Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
title_short Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
title_sort mutations of the ephb6 receptor tyrosine kinase induce a pro metastatic phenotype in non small cell lung cancer
url http://europepmc.org/articles/PMC3514309?pdf=render
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