Snail regulates cell-matrix adhesion by regulation of the expression of integrins and basement membrane proteins
Snail regulates cell-matrix adhesion by regulation of the expression of integrins and basement membrane proteins
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DOI：
10.1074/jbc.m801125200
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发表时间：
2008-08-29
影响因子：
4.8
通讯作者：
Ozawa, Masayuki
中科院分区：
文献类型：
--
作者：
Haraguchi, Misako;Okubo, Tadashi;Ozawa, Masayuki
Snail是E-cadherin表达的转录抑制因子，在上皮-间质转化过程中起作用。然而，蜗牛在上皮-间质转化中作用的分子基础尚未完全阐明。本研究表明，在上皮细胞Madin-Darby犬肾（MDCK）和A431细胞中，snail的表达增强了细胞的脱离和附着。蜗牛对失去接触引起的斑点病没有抵抗力，而是增强了细胞对细胞外基质（如纤维连接蛋白）的附着。Arg-Gly-Asp （RGD）肽抑制了这种附着。在表达MDCK （MDCK/snail）的蜗牛细胞中观察到整合素V启动子活性的上调。蜗牛还增强了MDCK细胞向骨桥蛋白的迁移，骨桥蛋白是整合素v3的配体。我们证实，在MDCK/蜗牛或蜗牛表达A431 （A431/蜗牛）细胞中，基底膜蛋白如层粘连蛋白(LN) α 3、β 3和γ 2 （laminin-5/LN-5）和LN-5受体如整合素α 3、α 6或α 4的减少。然而，瞬时转染小干扰rna对ln - γ - 3链的抑制并未导致细胞脱离的增强。我们还发现基质金属蛋白酶-3在MDCK/蜗牛和A431/蜗牛细胞中有诱导作用。然而，基质金属蛋白酶-3的抑制对MDCK/蜗牛细胞脱离无显著影响。这些结果表明，蜗牛通过多种机制增强细胞分离，并通过改变细胞中整合素的表达，至少在一定程度上导致细胞迁移和在第二位点的再附着。
Snail, a transcriptional repressor of E-cadherin expression, plays a role in the process of epithelial-mesenchymal transition. However, the molecular basis of the role of snail in epithelial-mesenchymal transition has not been fully clarified. Here we show that the expression of snail in epithelial Madin-Darby canine kidney (MDCK) and A431 cells enhances both cell detachment and attachment. Snail did not confer resistance to anoikis induced by loss of contact but instead enhanced cell attachment to extracellular matrices such as fibronectin. This attachment was inhibited by Arg-Gly-Asp (RGD) peptides. Up-regulation of the promoter activity of integrin V was observed in snail-expressing MDCK (MDCK/snail) cells. Snail also enhanced MDCK cell migration toward osteopontin that is a ligand for integrin V 3. We confirmed the reduction of basement membrane proteins such as laminin (LN) alpha 3, beta 3, and gamma 2 (laminin-5/LN-5) and of receptors for LN-5 such as integrins alpha 3, alpha 6, or alpha 4 in MDCK/snail or in snail-expressing A431 (A431/snail) cells. Nevertheless, suppression of LN-gamma 3 chain by transient transfection of small interference RNAs resulted in no enhancement of cell detachment. We also found an induction of matrix metalloproteinase-3 in MDCK/snail and A431/snailcells. However, the inhibition of matrix metalloproteinase-3 showed no significant effect on the detachment of MDCK/snail cells. These results suggest that snail enhances cell detachment by multiple mechanism and leads to cell migration and reattachment at a second site, at least in part, by changing the expression of integrins in the cells.