siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells
siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells
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DOI：
10.1002/ijc.21559
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发表时间：
2006-04-01
影响因子：
6.4
通讯作者：
Kuzumaki, N
中科院分区：
文献类型：
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作者：
Tanaka, H;Shirkoohi, R;Kuzumaki, N
上皮-间充质转化（EMT）描述了在发育和肿瘤发生期间发生的过程，通过该过程，上皮细胞获得成纤维细胞样性质并显示出降低的细胞粘附和增加的运动性。在这份报告中，我们证明了典型的EMT人乳腺上皮MCF 10A小干扰（si）RNA凝溶胶蛋白敲低细胞。EMT的特征为成纤维细胞形态、单层生长中接触抑制和病灶形成的丧失、体外运动性和侵袭性的增强、肌动蛋白丝的增加、RAC的过表达、细胞外信号调节激酶和AKT的激活、糖原合成酶激酶-3的失活、钙粘蛋白从E型向N型的转化以及转录因子Snail的诱导。这些结果表明，凝溶胶蛋白的功能作为一个开关，控制E-和N-钙粘蛋白转换通过蜗牛，并证明其敲低导致EMT在人类乳腺上皮细胞和可能的发展人类乳腺肿瘤。(c)2005 Wiley-Liss，Inc.
Epithelial-mesenchymal transition (EMT) describes a process occurring during development and oncogenesis by which epithelial cells obtain fibroblast-like properties and show reduced cell adhesion and increased motility. In this report, we demonstrated typical EMT in human mammary epithelial MCF10A small interfering (si)RNA gelsolin-knockdown cells. EMT was characterized by fibroblastic morphology, loss of contact inhibition and focus formation in monolayer growth, enhanced motility and invasiveness in vitro, increased actin filaments, overexpression of RAC, activation of both extracellular signal-regulated kinase and AKT, inactivation of glycogen synthase kinase-3, conversion of cadherin from the E- to N-type and induction of the transcription factor Snail. These results suggested that gelsolin functions as a switch that controls E- and N-cadherin conversion via Snail, and demonstrated that its knockdown leads to EMT in human mammary epithelial cells and possibly to the development of human mammary tumors. (c) 2005 Wiley-Liss, Inc.