The downstream of tyrosine kinase 7 is reduced in lung cancer and is associated with poor survival of patients with lung cancer

被引:13
作者
Chen, Gang [1 ,2 ,3 ,4 ]
Yu, Hefen [1 ,2 ,3 ]
Satherley, Lucy [4 ]
Zabkiewicz, Catherine [4 ]
Resaul, Jeyna [4 ]
Zhao, Huishan [1 ,2 ,3 ,4 ,5 ,6 ]
Mu, Hu [5 ]
Zhi, Xiuyi [5 ]
He, Junqi [1 ,2 ,3 ]
Ye, Lin [4 ]
Jiang, Wen G. [2 ,3 ,4 ]
机构
[1] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China
[2] Capital Med Univ, Canc Inst, Beijing 100069, Peoples R China
[3] Beijing Key Lab Canc Invas & Metastasis Res, Beijing 100069, Peoples R China
[4] Cardiff Univ, Sch Med, Cardiff China Med Res Collaborat, Heath Pk,Acad Ave, Cardiff CF14 4XN, S Glam, Wales
[5] Capital Med Univ, Xuanwu Hosp, Beijing 100053, Peoples R China
[6] Qingdao Univ, Coll Med, Affiliated Hosp, Cent Lab,Yantai Yuhuangding Hosp, Yantai 264000, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
downstream of tyrosine kinase 7; lung cancer; survival; adhesion and migration; CONGENITAL MYASTHENIA; DOK7; MUTATIONS; RECEPTOR; DOMAIN; MUSK; IDENTIFICATION; ACTIVATOR; SPECTRUM; AGRIN;
D O I
10.3892/or.2017.5538
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The downstream of tyrosine kinase 7 (DOK7) is an adaptor protein mediating signalling transduction between receptors and intracellular downstream molecules. Reduced expression of DOK7 has been observed in breast cancer. The present study aimed to investigate the role played by DOK7 in lung cancer. The expression of DOK7 at both mRNA and protein levels was evaluated in human lung cancer. A reduced expression of DOK7 transcripts was seen in lung cancers compared with normal lung tissues. Kaplan-Meier analyses showed that the reduced expression of DOK7 was associated with poorer overall survival and progression-free survival of patients with lung cancer. A further western blot analysis revealed a predominant expression of DOK7 isoform 1 (DOK7V1) in normal lung tissues, which was reduced in lung cancer. Forced overexpression of DOK7V1 in lung cancer cell lines, A549 and H3122 resulted in a decrease of in vitro cell proliferation and migration, while adhesion to extracellular matrix was enhanced following the expression. In conclusion, DOK7 was reduced in lung cancer and reduced DOK7 expression was associated with poorer survival. DOK7 isoform 1 plays an inhibitory role on the proliferation and migration of lung cancer cells in which Akt pathway may be involved.
引用
收藏
页码:2695 / 2701
页数:7
相关论文
共 29 条
[1]   Mutational and expressional analysis of a haploinsufficient tumor suppressor gene DOK2 in gastric and colorectal cancers [J].
An, Chang Hyeok ;
Kim, Min Sung ;
Yoo, Nam Jin ;
Lee, Sug Hyung .
APMIS, 2011, 119 (08) :562-564
[2]   Pleckstrin homology and phosphotyrosine-binding domain-dependent membrane association and tyrosine phosphorylation of Dok-4, an inhibitory adapter molecule expressed in epithelial cells [J].
Bedirian, A ;
Baldwin, C ;
Abe, J ;
Takano, T ;
Lemay, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (18) :19335-19349
[3]   The Cytoplasmic Adaptor Protein Dok7 Activates the Receptor Tyrosine Kinase MuSK via Dimerization [J].
Bergamin, Elisa ;
Hallock, Peter T. ;
Burden, Steven J. ;
Hubbard, Stevan R. .
MOLECULAR CELL, 2010, 39 (01) :100-109
[4]   Identification of DOK genes as lung tumor suppressors [J].
Berger, Alice H. ;
Niki, Masaru ;
Morotti, Alessandro ;
Taylor, Barry S. ;
Socci, Nicholas D. ;
Viale, Agnes ;
Brennan, Cameron ;
Szoke, Janos ;
Motoi, Noriko ;
Rothman, Paul B. ;
Teruya-Feldstein, Julie ;
Gerald, William L. ;
Ladanyi, Marc ;
Pandolfi, Pier Paolo .
NATURE GENETICS, 2010, 42 (03) :216-U27
[5]   Oncogenic kinase signalling [J].
Blume-Jensen, P ;
Hunter, T .
NATURE, 2001, 411 (6835) :355-365
[6]   An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors [J].
Chitale, D. ;
Gong, Y. ;
Taylor, B. S. ;
Broderick, S. ;
Brennan, C. ;
Somwar, R. ;
Golas, B. ;
Wang, L. ;
Motoi, N. ;
Szoke, J. ;
Reinersman, J. M. ;
Major, J. ;
Sander, C. ;
Seshan, V. E. ;
Zakowski, M. F. ;
Rusch, V. ;
Pao, W. ;
Gerald, W. ;
Ladanyi, M. .
ONCOGENE, 2009, 28 (31) :2773-2783
[7]   The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome [J].
Cossins, Judith ;
Liu, Wei Wei ;
Belaya, Katsiaryna ;
Maxwell, Susan ;
Oldridge, Michael ;
Lester, Tracy ;
Robb, Stephanie ;
Beeson, David .
HUMAN MOLECULAR GENETICS, 2012, 21 (17) :3765-3775
[8]   Dok-6, a novel p62 Dok family member, promotes Ret-mediated neurite outgrowth [J].
Crowder, RJ ;
Enomoto, H ;
Yang, M ;
Johnson, EM ;
Milbrandt, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (40) :42072-42081
[9]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[10]   Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation [J].
Grimm, J ;
Sachs, M ;
Britsch, S ;
Di Cesare, S ;
Schwarz-Romond, T ;
Alitalo, K ;
Birchmeier, W .
JOURNAL OF CELL BIOLOGY, 2001, 154 (02) :345-354