敲低上皮-间充质转化（EMT）主基因 ZEB1 可抑制肺癌细胞的无锚定依赖性细胞生长。
Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells.
机构信息
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
出版信息
Cancer Lett. 2010 Oct 28;296(2):216-24. doi: 10.1016/j.canlet.2010.04.008. Epub 2010 May 7.
Abstract
We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.
摘要
我们发现，在四个主要的上皮-间充质转化（EMT）诱导基因（ZEB1、SIP1、Snail 和 Slug）中，ZEB1 的表达与非小细胞肺癌（NSCLC）细胞系和肿瘤中的间充质表型（高波形蛋白和低 E-钙黏蛋白表达）最显著相关。此外，用 RNA 干扰在三个 ZEB1 高表达的 NSCLC 细胞系中敲低 ZEB1，在不同程度上抑制了大规模培养生长和液体集落形成，但在所有情况下都显著抑制了软琼脂集落形成。此外，在三条中的一条中，敲低 ZEB1 诱导了细胞凋亡，表明 ZEB1 敲低的生长抑制作用部分是通过激活凋亡途径发生的。这些结果表明，抑制 ZEB1 功能可能是 NSCLC 治疗开发的一个有吸引力的目标。
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