The effect of the RACK1 signalling protein on the regulation of cell adhesion and cell contact guidance on nanometric grooves
The effect of the RACK1 signalling protein on the regulation of cell adhesion and cell contact guidance on nanometric grooves
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DOI：
10.1016/j.biomaterials.2007.09.030
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发表时间：
2008-01-01
期刊：
影响因子：
14
通讯作者：
Yarwood, Stephen John
中科院分区：
文献类型：
--
作者：
Dalby, Matthew J.;Hart, Andrew;Yarwood, Stephen John
多种不同类型的细胞已被证明通过接触引导过程对纳米制造的生长表面作出反应，然而，对控制这些事件的细胞内机制知之甚少。在目前的研究中，我们已经确定了多功能信号适配器蛋白RACK1，作为定制工程纳米沟槽接触引导的新型负调节因子。我们发现RACK1在人乳腺癌细胞中的过度表达导致以应力纤维的形成和局灶性粘连为特征的亲粘附形态。RACK1的强制表达也限制了细胞对纳米沟槽接触引导的反应。相反，用特定的反义寡核苷酸消蚀RACK1蛋白会导致细胞在纳米深沟槽表面上的双向延伸显著增强，并相应失去局灶粘连和应力纤维。因此，RACK1对细胞接触引导发挥强直抑制作用，同时积极促进粘附表型。这是细胞内信号分子参与纳米生长表面细胞接触指导调控的第一个例子。(C) 2007 Elsevier Ltd.版权所有。
A wide variety of different cell types have been shown to respond to nanofabricated growth surfaces via the process of contact guidance, however little is known about the intracellular mechanisms that control these events. In the present study we have identified the multi-functional signalling adaptor protein, RACK1, as a novel negative regulator of contact guidance on custom-engineered nanometric grooves. We found that over-expression of RACK1 in human breast cancer cells leads to a pro-adherent morphology characterised by the formation of stress fibres and focal adhesions. Enforced expression of RACK1 also limits the response of cells to contact guidance on nanometric grooves. In contrast, ablation of RACK1 protein with specific anti-sense oligonucleotides led to a dramatic enhancement of bi-directional extension of cells on nanometrically deep grooved surfaces, with a corresponding loss of focal adhesions and stress fibres. RACK1 therefore exerts a tonic inhibitory effect on cell contact guidance, while positively promoting an adhesive phenotype. This is the first example of an intracellular signalling molecule involved in the regulation of cell contact guidance on nanometric growth surfaces. (C) 2007 Elsevier Ltd. All rights reserved.