Mutations of the EPHB6 Receptor Tyrosine Kinase Induce a Pro-Metastatic Phenotype in Non-Small Cell Lung Cancer

被引：24

作者：

Bulk, Etmar ^{[1
,2
]}

Yu, Jun ^{[1
,3
]}

Hascher, Antje ^{[1
]}

Koschmieder, Steffen ^{[1
]}

Wiewrodt, Rainer ^{[1
]}

Krug, Utz ^{[1
]}

Timmermann, Bernd ^{[4
]}

Marra, Alessandro ^{[5
]}

Hillejan, Ludger ^{[5
]}

Wiebe, Karsten ^{[6
]}

Berdel, Wolfgang E. ^{[1
]}

Schwab, Albrecht ^{[2
]}

Mueller-Tidow, Carsten ^{[1
]}

机构：

[1] Univ Munster, Dept Med Hematol A, Munster, Germany

[2] Univ Munster, Inst Physiol 2, Munster, Germany

[3] Fourth Mil Med Univ, Sch Basic Med Sci, Ctr Teaching Expt, Xian 710032, Shaanxi, Peoples R China

[4] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[5] Niels Stensen Hosp Ostercappeln, Dept Thorac Surg, Ostercappeln, Germany

[6] Univ Munster, Dept Thorac Surg, Munster, Germany

来源：

PLOS ONE | 2012年 / 7卷 / 12期

关键词：

BREAST-CARCINOMA CELLS; SOMATIC MUTATIONS; GENE-EXPRESSION; INVASIVENESS; PROMOTER; EPHRINS; EFNB2; STAGE; TRKA;

D O I：

10.1371/journal.pone.0044591

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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