Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin

被引:37
作者
Ferrand, A [1 ]
Kowalski-Chauvel, A [1 ]
Bertrand, C [1 ]
Pradayrol, L [1 ]
Fourmy, D [1 ]
Dufresne, M [1 ]
Seva, C [1 ]
机构
[1] Hop Rangueil, Inst Louis BUGNARD, Grp Recherche Biol & Pathol Digest, INSERM,U531, F-31059 Toulouse 9, France
关键词
JAK2; phosphatidylinositol; 3-kinase; cell-cell adhesion; gastrin;
D O I
10.1016/j.yexcr.2004.07.037
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway has been implicated in cell transformation and proliferation. Besides aberrant cell proliferation, loss of cell-cell adhesion during epithelial-mesenchymal transition (EMT) is an important event which occurs during development of epithelial cancers. However, the role of JAK-dependent pathways in this process is not known. We analyzed the involvement of these pathways in the regulation of E-cadherin-dependent cell-cell adhesion by gastrin, a mitogenic factor for gastrointestinal (GI) tract. We identified JAK2/STAT3 as a new pathway in gastrin signaling. We demonstrated that JAK2 functions as an upstream mediator of the phosphatidylinositol 3 (PI 3)-kinase activity in gastrin signaling. Indeed, we observed a coprecipitation of both kinases and an inhibition of gastrin-induced PI 3-kinase activation when JAK2 activity is blocked. We also demonstrated that loss of cell-cell adhesion and the increase in cell motility induced by gastrin required the activation of JAK2 and the PI 3-kinase. Indeed, the modifications in localization of adherens junctions proteins and the migration, observed in gastrin-stimulated cells, were reversed by inhibition of both kinases. These results described the involvement of JAK2 in the modulation of cell-cell adhesion in epithelial cells. They support a possible role of JAK2 in the epithelial-mesenchymal transition which occurs during malignant development. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:128 / 138
页数:11
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