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...
Main Authors: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1811268713418063872 |
---|---|
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. |
first_indexed | 2024-04-12T21:27:55Z |
format | Article |
id | doaj.art-555361feb8b7495f946ef0e5f27071ac |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T21:27:55Z |
publishDate | 2012-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT etmarbulk mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT junyu mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT antjehascher mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT steffenkoschmieder mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT rainerwiewrodt mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT utzkrug mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT berndtimmermann mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT alessandromarra mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT ludgerhillejan mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT karstenwiebe mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT wolfgangeberdel mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT albrechtschwab mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer AT carstenmullertidow mutationsoftheephb6receptortyrosinekinaseinduceaprometastaticphenotypeinnonsmallcelllungcancer |