The downstream of tyrosine kinase 7 is reduced in lung cancer and is associated with poor survival of patients with lung cancer.
The downstream of tyrosine kinase 7 is reduced in lung cancer and is associated with poor survival of patients with lung cancer.
复制标题
肺癌中酪氨酸激酶7的下游减少，与肺癌患者的生存率较差有关
DOI：
10.3892/or.2017.5538
复制
发表时间：
2017-05
期刊：
影响因子：
4.2
通讯作者：
Jiang WG
中科院分区：
文献类型：
--
作者：
Chen G;Yu H;Satherley L;Zabkiewicz C;Resaul J;Zhao H;Mu H;Zhi X;He J;Ye L;Jiang WG
酪氨酸激酶7（DOK 7）的下游是介导受体和细胞内下游分子之间的信号转导的衔接蛋白。已经在乳腺癌中观察到DOK 7的表达降低。本研究旨在探讨DOK 7在肺癌中的作用。在mRNA和蛋白质水平上评估人肺癌中DOK 7的表达。与正常肺组织相比，在肺癌中观察到DOK 7转录物的表达降低。Kaplan-Meier分析显示，DOK 7表达降低与肺癌患者的总生存率和无进展生存率相关。进一步的蛋白质印迹分析揭示了DOK 7同种型1（DOK 7V 1）在正常肺组织中的主要表达，其在肺癌中降低。DOK 7V 1在肺癌细胞系A549和H3122中的强制过表达导致体外细胞增殖和迁移的减少，而表达后与细胞外基质的粘附增强。总之，DOK 7在肺癌中减少，并且DOK 7表达减少与较差的存活率相关。DOK 7亚型1对肺癌细胞的增殖和迁移具有抑制作用，可能与Akt通路有关。
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.