Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells
Involvement of LKB1 in epithelial-mesenchymal transition (EMT) of human lung cancer cells
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DOI：
10.1016/j.lungcan.2010.02.004
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发表时间：
2010-11-01
期刊：
影响因子：
5.3
通讯作者：
Yokota, Jun
中科院分区：
文献类型：
--
作者：
Roy, Badal C.;Kohno, Takashi;Yokota, Jun
上皮间质转化（EMT）是癌细胞的一种重要表型改变，它触发了癌细胞的侵袭和转移。肺癌细胞通常显示间充质表型;然而，肺癌细胞中诱导EMT的致病性遗传改变仍然未知。最近的研究表明，LKB 1基因在多达三分之一的肺腺癌中发生突变。因此，为了研究LKB 1失活在肺癌发生中诱导EMT中的可能参与，我们产生了具有稳定或瞬时LKB 1敲低的永生化肺上皮细胞和肺腺癌细胞。LKB 1敲低增加细胞运动性和侵袭性，并诱导几种间充质标志物蛋白的表达，伴随着ZEB 1的表达，ZEB 1是E-钙粘蛋白的转录抑制因子和EMT诱导剂。与最近的研究结果一致，在具有间充质表型的LKB 1敲除克隆中，miR-200 a/c的表达与ZEB 1的表达呈负相关。此外，瞬时敲低LKB 1诱导ZEB 1 mRNA和增加细胞运动性，这种运动性被ZEB 1阻遏所抑制。这些结果强烈表明LKB 1失活通过诱导ZEB 1触发肺癌细胞中的EMT。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Epithelial mesenchymal transition (EMT) is a critical phenotypic alteration of cancer cells that triggers invasion and metastasis. Lung cancer cells often show mesenchymal phenotypes; however, a causative genetic alteration for the induction of EMT in lung cancer cells remains unknown. Recent studies have shown that the LKB1 gene is mutated in up to one-third of lung adenocarcinomas. Therefore, to pursue the possible involvement of LKB1 inactivation in the induction of EMT in lung carcinogenesis, we generated immortalized lung epithelial cells and lung adenocarcinoma cells with stable or transient LKB1 knockdown. LKB1 knockdown increased cell motility and invasiveness, and induced the expression of several mesenchymal marker proteins accompanied by the expression of ZEB1, a transcriptional repressor for E-cadherin and an EMT inducer. In agreement with the recent findings, expression of miR-200a/c was inversely correlated with that of ZEB1 in LKB1 knockdown clones with mesenchymal phenotype. Furthermore, transient knockdown of LKB1 induced ZEB1 mRNA and increased cell motility, and this motility was suppressed by ZEB1 repression. These results strongly indicate that LKB1 inactivation triggers EMT in lung cancer cells through the induction of ZEB1. (C) 2010 Elsevier Ireland Ltd. All rights reserved.