Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells.
Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells.
复制标题
MTA1的表达促进了PANC-1胰腺癌细胞的运动和侵袭性。
DOI：
10.1038/sj.bjc.6601535
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发表时间：
2004-01-26
影响因子：
8.8
通讯作者：
Giehl, K
中科院分区：
文献类型：
--
作者：
Hofer, M D;Menke, A;Genze, F;Gierschik, P;Giehl, K
人类转移相关蛋白1(MTA1)是核小体重塑和脱乙酰基复合体的组成部分。其表达与上皮性肿瘤的侵袭转移密切相关。为了解决MTA1在胰腺癌细胞中表达的功能后果，我们建立了稳定表达MTA1作为增强型绿色荧光融合蛋白(EGFP-MTA1)的PANC-1胰腺癌细胞。在这里，我们证明了异源表达EGFP-MTA1显著增强了细胞的运动性和细胞对上皮屏障的侵袭穿透。EGFP-MTA1的表达对底物非依赖性生长没有影响，但抑制了底物依赖性细胞的增殖。此外，在表达EGFP-MTA1的细胞中，细胞角蛋白细丝系统的组织和肌动蛋白细胞骨架相关蛋白IQGAP1的定位明显改变。这些结果表明，MTA1的表达增强促进了侵袭性、转移性表型的获得，从而通过调节细胞骨架增强了胰腺癌细胞的恶性程度。
The human metastasis-associated protein 1 (MTA1) is a constituent of the nucleosome-remodelling and -deacetylation complex. Its expression has been correlated with the invasion and metastasis of epithelial neoplasms. To address the functional consequences of MTA1 expression in pancreatic carcinoma cells, we have established PANC-1 pancreatic carcinoma cells that stably express MTA1 as an enhanced green fluorescent fusion protein (EGFP–MTA1). Here, we demonstrate that heterologous expression of EGFP–MTA1 markedly enhanced the cellular motility and the invasive penetration of epithelial barriers by the cells. Expression of EGFP-MTA1 had no effect on substrate-independent growth, but reduced substrate-dependent cell proliferation. In addition, the organisation of the cytokeratin filament system and the localisation of the actin cytoskeleton-associated protein IQGAP1 were distinctly altered in EGFP–MTA1-expressing cells. These results indicate that enhanced expression of MTA1 promotes the acquisition of an invasive, metastatic phenotype, and thus enhances the malignancy of pancreatic adenocarcinoma cells by modulation of the cytoskeleton.