Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation.

Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation.
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LASP-1 的过度表达介导人卵巢癌细胞的迁移和增殖并影响 zyxin 定位。

DOI:
10.1038/sj.bjc.6603545
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发表时间:
2007-01-29
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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LIM和SH3蛋白1(LASP-1)最初是从人类乳腺癌中鉴定出来的,是一种参与细胞增殖和迁移的特定局灶性粘合剂蛋白,我们分析了LASP-1对人类生物学和人类功能的影响。使用小型干扰RNA技术(siRNA)的卵巢癌细胞系SKOV-3。与LASP-1特异性siRNA转染导致SKOV-3细胞中的LASP-1蛋白质水平降低。 M抑制了60-90%的细胞周期和肿瘤细胞的增殖沉默伴随着LASP-1结合伴侣Zyxin与局灶性接触的结合,而肌动蛋白应力纤维和微管组织的变化或局灶性粘合形态的变化相反,与免疫荧光相反,Zyxin的沉默并不影响细胞移民。对LASP-1表达或肌动蛋白细胞骨架的影响和局灶性接触形态既不表明LASP-1对于募集Zyxin进行局灶性接触是必要的,并且足够足够。通过影响Zyxin定位。
LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration. In the present work, we analysed the effect of LASP-1 on biology and function of human ovarian cancer cell line SKOV-3 using small interfering RNA technique (siRNA).Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G2/M phase of the cell cycle and proliferation of the tumour cells was suppressed by 60–90% corresponding to around 70% of the cells being transfected successfully as seen by immunofluorescence. Moreover, transfected tumour cells showed a 40% reduced migration. LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence. In contrast, silencing of zyxin is not influencing cell migration and had neither influence on LASP-1 expression nor actin cytoskeleton and focal contact morphology suggesting that LASP-1 is necessary and sufficient for recruiting zyxin to focal contacts.The data provide evidence for an essential role of LASP-1 in tumour cell growth and migration, possibly through influencing zyxin localization.
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