Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas.
Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas.
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Gli促进人肺腺癌上皮间质转化
DOI：
10.18632/oncotarget.11246
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发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
He B
中科院分区：
文献类型：
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作者：
Li H;Yue D;Jin JQ;Woodard GA;Tolani B;Luh TM;Giroux-Leprieur E;Mo M;Chen Z;Che J;Zhang Z;Zhou Y;Wang L;Hao X;Jablons D;Wang C;He B
腺癌是最常见的肺癌类型。上皮-间质转化（EMT）是肿瘤侵袭/转移所必需的，控制这一过程的组分是潜在的治疗靶点。本研究探讨了Gli在肺腺癌中的作用，以及其激活是否通过肺腺癌中的EMT调节转移。我们发现，在我们研究的两个独立的肺腺癌患者队列中，Gli高表达的肿瘤具有显著较低的E-Cadherin表达。在体外上调SHh导致增加的细胞迁移，而Smo或Gli的小分子抑制剂显着降低细胞的流动性，在伤口愈合试验和3D细胞侵袭试验。体内抑制Gli可降低肿瘤生长并诱导E-钙粘蛋白表达增加。我们的研究结果表明，Gli可能是肺腺癌转移的关键，一种新的Gli抑制剂显示出作为一种治疗剂，通过防止细胞迁移和体外侵袭，显着降低肿瘤生长和增加E-钙粘蛋白表达在体内的承诺。
Adenocarcinoma is the most common type of lung cancer. Epithelial-mesenchymal transition (EMT) is required for tumor invasion/metastasis and the components that control this process are potential therapeutic targets. This study we examined the role of Gli in lung adenocarcinoma and whether its activation regulates metastasis through EMT in lung adenocarcinoma. We found that tumors with high Gli expression had significantly lower E-Cadherin expression in two independent cohorts of patients with lung adenocarcinoma that we studied. In vitro up-regulation of SHh resulted in increased cell migration while small molecule inhibitors of Smo or Gli significantly reduced cell mobility both in a wound healing assay and in a 3D cell invasion assay. Inhibition of Gli in vivo decreased tumor growth and induced an increase in E-Cadherin expression. Our results indicate that Gli may be critical for lung adenocarcinoma metastasis and that a novel Gli inhibitor shows promise as a therapeutic agent by preventing cell migration and invasion in vitro and significantly reducing tumor growth and increasing E-Cadherin expression in vivo.