The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells
The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells
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DOI：
10.1007/s00018-010-0395-6
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发表时间：
2010-10-01
影响因子：
8
通讯作者：
Dvorak, Michal
中科院分区：
文献类型：
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作者：
Cermak, Vladimir;Kosla, Jan;Dvorak, Michal
癌细胞的转移性扩散是一个高度复杂的过程，主要由肿瘤微环境、细胞表面受体和肌动蛋白细胞骨架动力学之间的相互作用决定。为了加深我们对转移性癌症传播的理解，我们开发了一个基于两种 v-src 转化的鸡肉瘤细胞系的模型系统 - 高度转移的亲本 PR9692 和非转移但完全致瘤的克隆衍生物 PR9692-E9。对两种细胞系的寡核苷酸微阵列分析表明，编码转录因子 EGR1 的基因在非转移性 PR9692-E9 细胞中下调。进一步的研究表明，将外源 EGR1 引入 PR9692-E9 细胞可将其转移潜力恢复到与亲代 PR9692 细胞无法区分的水平。 EGR1 重组细胞的微阵列分析揭示了对肌动蛋白细胞骨架收缩性 (MYL9)、丝状伪足形成 (MYO10)、特定细胞外基质成分 (HAS2、COL6A1-3) 的产生和其他重要的促转移能力至关重要的基因的激活。
Metastatic spreading of cancer cells is a highly complex process directed primarily by the interplay between tumor microenvironment, cell surface receptors, and actin cytoskeleton dynamics. To advance our understanding of metastatic cancer dissemination, we have developed a model system that is based on two v-src transformed chicken sarcoma cell lines-the highly metastatic parental PR9692 and a non-metastasizing but fully tumorigenic clonal derivative PR9692-E9. Oligonucleotide microarray analysis of both cell lines revealed that the gene encoding the transcription factor EGR1 was downregulated in the non-metastatic PR9692-E9 cells. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from parental PR9692 cells. Microarray analysis of EGR1 reconstituted cells revealed the activation of genes that are crucial for actin cytoskeleton contractility (MYL9), filopodia formation (MYO10), the production of specific extracellular matrix components (HAS2, COL6A1-3) and other essential pro-metastatic abilities.