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

Chen,Gang; Yu,Hefen; Satherley,Lucy; Zabkiewicz,Catherine; Resaul,Jeyna; Zhao,Huishan; Mu,Hu; Zhi,Xiuyi; He,Junqi; Ye,Lin; Jiang,Wen  G.

doi:10.3892/or.2017.5538

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

Authors:
- Gang Chen
- Hefen Yu
- Lucy Satherley
- Catherine Zabkiewicz
- Jeyna Resaul
- Huishan Zhao
- Hu Mu
- Xiuyi Zhi
- Junqi He
- Lin Ye
- Wen G. Jiang
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China, Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK, Xuanwu Hospital Capital Medical University, Beijing 100053, P.R. China, Cancer Institute of Capital Medical University, Beijing 100069, P.R. China
Published online on: March 31, 2017 https://doi.org/10.3892/or.2017.5538
Pages: 2695-2701
Copyright : © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

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.

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