共 48 条
The tandem PDZ domains of syntenin promote cell invasion
被引:37
作者:

Meerschaert, Kris
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Bruyneel, Erik
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

De Wever, Olivier
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Vanloo, Berlinda
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Boucherie, Ciska
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Bracke, Marc
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Vandekerckhove, Joel
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium

Gettemans, Jan
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机构: Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium
机构:
[1] Univ Ghent, Fac Med & Hlth Sci, Dept Med Prot Res, VIB, B-9000 Ghent, Belgium
[2] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium
[3] Ghent Univ Hosp 1P7, Expt Cancerol Lab, Dept Radiotherapy & Nucl Med, B-9000 Ghent, Belgium
关键词:
syntenin;
PDZ domain;
phosphoinositide;
invasion;
signal transduction;
cell adhesion;
D O I:
10.1016/j.yexcr.2007.03.014
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Syntenin is a tandem PDZ protein that has recently been shown to be overexpressed in several cancer cells and tissues, and that might play an active role in tumor cell invasion and metastasis. Here we show that overexpression of the tandem PDZ domains of syntenin in non-invasive cells is necessary and sufficient to stimulate these cells to invade a collagen I matrix, and this effect can be regulated by ligand binding to the PDZ domains. Furthermore, we show that syntenin-induced invasion requires signaling through ras, rho and PI3K/MAPK signaling pathways and involves changes in cell-cell adhesion. Inversely, when we used RNA interference to inhibit syntenin expression in different invasive cancer cell lines, we observed a drastically decreased ability of these cells to migrate and invade into collagen type I or Matrigel (R). RNAi-tyeated cells also show increased cell aggregation, indicating that syntenin is important for cell-cell adhesion in epithelial cells. Together, these results suggest that downregulation of syntenin by RNA interference could provide a means of inhibiting tumor invasion and possibly metastasis in different cancers, and point to syntenin as a potential cancer biomarker and drug target. (c) 2007 Elsevier Inc. All rights reserved.
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页码:1790 / 1804
页数:15
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