期刊
EXPERIMENTAL CELL RESEARCH
卷 317, 期 2, 页码 195-209出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2010.10.003
关键词
ADAM 12; Invadopodia; Src; beta 3 integrin; Lipid rafts; Ectodomain shedding
资金
- Danish Cancer Society
- Danish Medical Research Council
- Friis Foundation
- Munksholm Foundation
- Novo Nordisk Foundation
lnvadopodia are dynamic actin structures at the cell surface that degrade extracellular matrix and act as sites of signal transduction. The biogenesis of invadopodia, including the mechanisms regulating their formation, composition, and turnover is not entirely understood. Here, we demonstrate that antibody ligation of ADAM12, a transmembrane disintegrin and metalloprotease, resulted in the rapid accumulation of invadopodia with extracellular matrix-degrading capacity in epithelial cells expressing the alpha v beta 3 integrin and active c-Src kinase. The induction of invadopodia clusters required an intact c-Src interaction site in the ADAM12 cytoplasmic domain, but was independent of the catalytic activity of ADAM12. Caveolin-1 and transmembrane protease MMP14/MT1-MMP were both present in the ADAM12-induced clusters of invadopodia, and cholesterol depletion prevented their formation, suggesting that lipid-raft microdomains are involved in the process. Importantly, our data demonstrate that ADAM12-mediated ectodomain shedding of epidermal growth factor receptor ligands can occur within these invadopodia. Such localized growth factor signalling offers an interesting novel biological concept highly relevant to the properties of carcinoma cells, which often show upregulated ADAM 12 and 133 integrin expression, together with high levels of c-Src kinase activity. (C) 2010 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据