Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI
Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI
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DOI：
10.1038/labinvest.2016.77
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发表时间：
2016-09-01
影响因子：
5
通讯作者：
Gottfried, Maya
中科院分区：
文献类型：
--
作者：
Attar-Schneider, Oshrat;Drucker, Liat;Gottfried, Maya
转移是癌症发病的基础，通常是疾病进展和显着死亡率的原因，特别是在非小细胞肺癌（NSCLC）中。因此，了解调节转移的分子事件至关重要。不断积累的数据表明蛋白质合成，特别是翻译起始 (TI) 因子 eIF4E 和 eIF4G 在肿瘤发生和患者生存中发挥着核心作用。我们已经发表了 eIF4E/eIF4GI 活性以及随之而来的 NSCLC 细胞迁移受到骨髓间充质干细胞分泌组的调节，这表明 TI 在转移中的作用。在这里，我们的目的是扩大我们对 TI 因素对 NSCLC 特征的重要性的理解，特别是上皮间质转化 (EMT) 和迁移，支持转移。在 NSCLC 细胞系（H1299、H460）模型中，我们抑制 eIF4E/eIF4GI 的表达（siRNA、利巴韦林）并评估 NSCLC 细胞系的迁移（划痕）、分化（EMT、免疫印迹）和选定 microRNA 的表达 (qPCR)。最初，我们确定了与正常肺样本相比，NSCLC 中几种 TI 因子（eIF4E、eIF4GI、eIF4B 和 DHX29）及其各自靶标的过度表达（70-350% 向上箭头，P
Metastasis underlies cancer morbidity and accounts for disease progression and significant death rates generally and in non-small cell lung cancer (NSCLC) particularly. Therefore, it is critically important to understand the molecular events that regulate metastasis. Accumulating data portray a central role for protein synthesis, particularly translation initiation (TI) factors eIF4E and eIF4G in tumorigenesis and patients' survival. We have published that eIF4E/eIF4GI activities and consequently NSCLC cell migration are modulated by bone-marrow mesenchymal stem cell secretomes, suggesting a role for TI in metastasis. Here, we aimed to expand our understanding of the TI factors significance to NSCLC characteristics, particularly epithelial-to-mesenchymal transition (EMT) and migration, supportive of metastasis. In a model of NSCLC cell lines (H1299, H460), we inhibited eIF4E/eIF4GI's expressions (siRNA, ribavirin) and assessed NSCLC cell lines' migration (scratch), differentiation (EMT, immunoblotting), and expression of select microRNAs (qPCR). Initially, we determined an overexpression of several TI factors (eIF4E, eIF4GI, eIF4B, and DHX29) and their respective targets in NSCLC compared with normal lung samples (70-350%up arrow, P