A transient increase in the activity of Src-family kinases induced by cell detachment delays anoikis of intestinal epithelial cells
A transient increase in the activity of Src-family kinases induced by cell detachment delays anoikis of intestinal epithelial cells
复制标题
DOI：
10.1038/sj.onc.1208379
复制
发表时间：
2005-03-03
期刊：
影响因子：
8
通讯作者：
Filmus, J
中科院分区：
文献类型：
--
作者：
Coll, MAL;Perera, S;Filmus, J
上皮细胞从基底膜（BM）上脱落诱导细胞凋亡，这种现象现在被广泛称为失巢凋亡。对乳腺和肠上皮细胞的研究表明，与BM的附着丧失迅速触发可逆的促凋亡事件，如果细胞在一定时间内重新附着，则细胞可以从中恢复。因此，细胞似乎是短暂的保护，从最初的凋亡诱导的促凋亡事件。这种针对失巢凋亡的瞬时保护的分子机制尚不清楚。在本文中，我们提出的证据表明，脱离肠上皮细胞触发一个短暂的，但显着增加的酪氨酸激酶c-Src和c-Fyn的活性，这种Src家族激酶（SFK）的激活有助于对失巢凋亡在这些细胞的瞬时保护。来自SFK的保护信号由PI 3 K通路和小窝蛋白-1介导。此外，我们发现MEK 1-ERK 1/2通路与SFK以协同方式起作用，以保护肠上皮细胞免受失巢凋亡。
Detachment of epithelial cells from the basement membrane ( BM) induces apoptosis, a phenomenon now widely known as anoikis. Studies in mammary and intestinal epithelial cells have shown that the loss of attachment to the BM rapidly triggers reversible proapoptotic events from which the cells can recover if they reattach within a certain period. Thus, cells seem to be transiently protected from the initial detachment-induced proapoptotic events. The molecular mechanisms underlying such transient protection against anoikis are unknown. In this paper, we present evidence indicating that detachment of intestinal epithelial cells triggers a transient, yet significant increase in the activity of the tyrosine kinases c-Src and c-Fyn, and that this activation of Src-family kinases (SFK) contributes to the transient protection against anoikis in these cells. The protective signals from SFK are mediated by the PI3K pathway, and caveolin-1. In addition, we show that the MEK1-ERK1/2 pathway acts in a synergistic manner with SFK to protect intestinal epithelial cells from anoikis.