Role of zyxin in differential cell spreading and proliferation of melanoma cells and melanocytes
Role of zyxin in differential cell spreading and proliferation of melanoma cells and melanocytes
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DOI：
10.1046/j.0022-202x.2001.01657.x
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发表时间：
2002-02-01
影响因子：
6.5
通讯作者：
Byers, HR
中科院分区：
文献类型：
--
作者：
van der Gaag, EJ;Leccia, MT;Byers, HR
细胞的扩散、增殖和存活受连接细胞外基质蛋白、整合素和细胞骨架的粘着斑调节。Zyxin是一种局灶性粘附相关磷蛋白，具有一个参与控制肌动蛋白组装的结构域和三个参与调节细胞生长和分化的蛋白质-蛋白质衔接子结构域。我们的特点zyxin在正常人黑素细胞和6个黑色素瘤细胞系的细胞扩散，生长和分化，使用Western免疫印迹技术，图像分析，流式细胞术，共聚焦显微镜。我们发现，zyxin，粘着斑激酶，桩蛋白显着上调黑色素瘤细胞相比，黑素细胞。Zyxin的表达与细胞的扩散和增殖直接相关，与分化呈负相关，而粘着斑激酶仅与细胞扩散相关，桩蛋白与任何参数均无显著相关性。用12-O-十四酰基佛波醇-13-乙酸酯处理黑色素瘤细胞下调zyxin表达，抑制细胞扩散和增殖，并促进分化。相反，12-O-十四酰基佛波醇-13-乙酸酯，黑素细胞的有丝分裂原，诱导黑素细胞zyxin表达上调。这些发现与zyxin在调节细胞铺展、增殖和分化中的作用一致。针对黑色素瘤细胞中这种粘着斑磷蛋白的下调的治疗涉及控制黑色素瘤细胞生长的新方法。
Cell spreading, proliferation, and survival are modulated by focal adhesions linking extracellular matrix proteins, integrins, and the cytoskeleton. Zyxin is a focal-adhesion-associated phosphoprotein with one domain involved in the control of actin assembly and three protein-protein adapter domains implicated in the regulation of cell growth and differentiation. We characterized zyxin expression in normal human melanocytes and six melanoma cell lines in relation to cell spreading, growth, and differentiation using Western immunoblotting techniques, image analysis, flow cytometry, and confocal microscopy. We found that zyxin, focal adhesion kinase, and paxillin were significantly upregulated in melanoma cells compared to melanocytes. Zyxin expression directly related to cell spreading and proliferation and inversely related to differentiation, whereas focal adhesion kinase correlated only to cell spreading and paxillin did not significantly correlate with any of the parameters. Treatment of melanoma cells with 12-O-tetradecanoylphorbol-13-acetate downregulated zyxin expression, inhibited cell spreading and proliferation, and promoted differentiation. In contrast, 12-O-tetradecanoylphorbol-13-acetate, a mitogen for melanocytes, induced upregulation of zyxin expression in melanocytes. These findings are consistent with a role of zyxin in modulation of cell spreading, proliferation, and differentiation. Therapies directed at the downregulation of this focal adhesion phosphoprotein in melanoma cells implicate a now approach for controlling melanoma cell growth.