Novel c-MYC target genes mediate differential effects on cell proliferation and migration
Novel c-MYC target genes mediate differential effects on cell proliferation and migration
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DOI：
10.1038/sj.embor.7400849
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发表时间：
2007-01-01
期刊：
影响因子：
7.7
通讯作者：
Hynes, Nancy E.
中科院分区：
文献类型：
--
作者：
Cappellen, David;Schlange, Thomas;Hynes, Nancy E.
MYC蛋白的发育和致癌作用已经得到了很好的证实，但是介导其功能的转录靶点仍然难以捉摸。在乳腺癌和宫颈癌细胞系中使用小干扰RNA介导的敲除，其过表达c-MYC，我们表明c-MYC独立地控制代谢和细胞增殖，并且可以根据细胞促进或抑制迁移。我们在这些细胞系中鉴定了新的c-MYC靶基因，并表明某些靶基因的选择性调节与这些不同细胞系对c-MYC耗竭的表型反应相关。值得注意的是，我们表明，WNT信号通路的正调控有助于c-MYC促进乳腺癌和宫颈癌细胞的促有丝分裂作用。我们还表明，CCL 5/RANTES的抑制占c-MYC抗迁移作用在特定的乳腺癌细胞。我们结合基因组和表型分析表明，c-MYC功能是细胞环境依赖性的，选择性调节基因是其差异特性的原因。
The developmental and oncogenic roles of MYC proteins are well established, but the transcriptional targets mediating their functions remain elusive. Using small interfering RNA-mediated knockdown in breast and cervix carcinoma cell lines, which overexpress c-MYC, we show that c-MYC independently controls metabolism and cell proliferation, and can, depending on the cells, promote or inhibit migration. We identified new c-MYC target genes in these cell lines, and show that selective regulation of some targets correlates with the phenotypic responses of these different cell lines to c-MYC depletion. Notably, we show that a positive regulation of the WNT signalling pathway contributes to c-MYC pro-mitogenic effects in breast and cervix carcinoma cells. We also show that repression of CCL5/RANTES accounts for c-MYC anti-migratory effects in specific breast cancer cells. Our combined genomic and phenotypic analysis indicates that c-MYC functions are cellular-context-dependent and that selectively regulated genes are responsible for its differential properties.