OCT1 is a determinant of synbindin-related ERK signalling with independent prognostic significance in gastric cancer.
OCT1 is a determinant of synbindin-related ERK signalling with independent prognostic significance in gastric cancer.
复制标题
DOI：
10.1136/gutjnl-2013-306584
复制
发表时间：
2015-01
期刊：
影响因子：
24.5
通讯作者：
Fang JY
中科院分区：
文献类型：
--
作者：
Qian J;Kong X;Deng N;Tan P;Chen H;Wang J;Li Z;Hu Y;Zou W;Xu J;Fang JY
八聚体转录因子1（Octamer transcription factor 1，OCT 1）在肠上皮化生和胃癌中有表达，但其在胃癌中的确切作用尚不清楚。本研究的目的是确定OCT 1在GC中的功能和预后意义。在配对的正常和胃癌组织中检测OCT 1的表达，并通过单因素和多因素生存分析来分析OCT 1的预后意义。在体外和异种移植小鼠模型中研究了OCT 1对synbindin表达和细胞外信号调节激酶（ERK）磷酸化的功能。OCT 1基因在GC中反复扩增和上调。OCT 1过表达和扩增与GC患者的不良生存率相关，独立患者队列证实了其预后意义。OCT 1过表达与美国癌症联合委员会分期相结合可提高GC患者生存率的预测。胃癌组织中OCT 1的高表达与ERK丝裂原活化蛋白激酶信号通路的激活有关。OCT 1通过反式激活synbindin发挥作用，synbindin结合ERK DEF结构域并促进MEK对ERK的磷酸化。OCT 1-synbindin信号转导导致ERK底物ELK 1和RSK的活化，导致细胞增殖和侵袭增加。人胃癌组织样本的免疫荧光研究显示OCT 1蛋白水平与synbindin表达/ERK磷酸化之间存在强相关性。在小鼠异种移植模型中上调OCT 1诱导synbindin表达和ERK激活，导致体内肿瘤生长加速。OCT 1是synbindin介导的ERK信号传导的驱动因子，也是GC预后和分子亚型的有希望的标志物。
Octamer transcription factor 1 (OCT1) was found to be expressed in intestinal metaplasia and gastric cancer (GC), but the exact roles of OCT1 in GC remain unclear. The objective of this study was to determine the functional and prognostic implications of OCT1 in GC. Expression of OCT1 was examined in paired normal and cancerous gastric tissues and the prognostic significance of OCT1 was analysed by univariate and multivariate survival analyses. The functions of OCT1 on synbindin expression and extracellular signal-regulated kinase (ERK) phosphorylation were studied in vitro and in xenograft mouse models. The OCT1 gene is recurrently amplified and upregulated in GC. OCT1 overexpression and amplification are associated with poor survival in patients with GC and the prognostic significance was confirmed by independent patient cohorts. Combining OCT1 overexpression with American Joint Committee on Cancer staging improved the prediction of survival in patients with GC. High expression of OCT1 associates with activation of the ERK mitogen-activated protein kinase signalling pathway in GC tissues. OCT1 functions by transactivating synbindin, which binds to ERK DEF domain and facilitates ERK phosphorylation by MEK. OCT1-synbindin signalling results in the activation of ERK substrates ELK1 and RSK, leading to increased cell proliferation and invasion. Immunofluorescent study of human GC tissue samples revealed strong association between OCT1 protein level and synbindin expression/ERK phosphorylation. Upregulation of OCT1 in mouse xenograft models induced synbindin expression and ERK activation, leading to accelerated tumour growth in vivo. OCT1 is a driver of synbindin-mediated ERK signalling and a promising marker for the prognosis and molecular subtyping of GC.
登录
查看更多内容
影响因子：
24.5
作者：
Deng N;Goh LK;Wang H;Das K;Tao J;Tan IB;Zhang S;Lee M;Wu J;Lim KH;Lei Z;Goh G;Lim QY;Tan AL;Sin Poh DY;Riahi S;Bell S;Shi MM;Linnartz R;Zhu F;Yeoh KG;Toh HC;Yong WP;Cheong HC;Rha SY;Boussioutas A;Grabsch H;Rozen S;Tan P
通讯作者：
Tan P
影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2013.06.114
发表时间：
2013-08-09
影响因子：
3.1
作者：
Ahn, Hee-Jin;Kim, Gwangil;Park, Kyung-Soon
通讯作者：
Park, Kyung-Soon
影响因子：
24.5
作者：
Coupland, Victoria H.;Lagergren, Jesper;Moller, Henrik
通讯作者：
Moller, Henrik
影响因子：
11.2
作者：
Dulak AM;Schumacher SE;van Lieshout J;Imamura Y;Fox C;Shim B;Ramos AH;Saksena G;Baca SC;Baselga J;Tabernero J;Barretina J;Enzinger PC;Corso G;Roviello F;Lin L;Bandla S;Luketich JD;Pennathur A;Meyerson M;Ogino S;Shivdasani RA;Beer DG;Godfrey TE;Beroukhim R;Bass AJ
通讯作者：
Bass AJ