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首页> 外文期刊>Molecular and Cellular Biology >Nucleosome Remodeler SNF2L Suppresses Cell Proliferation and Migration and Attenuates Wnt Signaling
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Nucleosome Remodeler SNF2L Suppresses Cell Proliferation and Migration and Attenuates Wnt Signaling

机译:核小体重塑剂SNF2L抑制细胞增殖和迁移并减弱Wnt信号传导

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ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells.
机译:ISWI是一种进化上保守的ATPase,可催化不同大分子复合物中的核小体重塑。尽管两个ISWI直系同源物SNF2H和SNF2L具有高度的序列相似性,但它们仍具有特殊的功能。迄今为止,SNF2L在人细胞中的功能尚未成为研究的重点。新建立的特异性单克隆抗体和选择性RNA干扰方案现已使人细胞功能丧失表型的全面表征成为可能。与早期结果相反,我们发现SNF2L在原代人组织中广泛表达。 HeLa细胞中SNF2L的耗尽导致增殖增强和迁移增加。这些现象可以通过转录组分析来解释,转录组分析将SNF2L鉴定为Wnt信号网络的调节剂。 SNF2L耗竭对基因表达的累积影响描绘了细胞处于激活的Wnt信号传导状态,其特征是增殖和趋化运动增加。因此,正常黑素细胞中高水平的SNF2L表达与恶性黑素瘤中无法检测到的表达形成对比。总之,我们的数据记录了SNF2L表达与恶性细胞特征之间的反比关系。

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