DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail
DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail
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DOI：
10.1111/cas.13997
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发表时间：
2019-05-01
期刊：
影响因子：
5.7
通讯作者：
Sakakibara-Konishi, Jun
中科院分区：
文献类型：
--
作者：
Furuta, Megumi;Kikuchi, Hajime;Sakakibara-Konishi, Jun
Delta样蛋白3（DLL 3）是Notch信号传导的配体，其介导细胞命运决定，并且根据细胞环境是肿瘤抑制的或致癌的。以前的研究表明，DLL 3在小细胞肺癌（SCLC）中高表达，而在正常肺组织中不表达，这表明DLL 3可能与神经内分泌肿瘤的发生有关。然而，它在南方基督教领袖会议中的作用仍不清楚。为了研究DLL 3在SCLC肿瘤发生中的作用，我们使用SCLC细胞系进行了功能丧失和功能获得测定。通过transwell测定的细胞迁移和侵袭的体外分析表明，DLL 3敲低降低了SCLC细胞的迁移和侵袭，而DLL 3过表达增加了这些活性。此外，DLL 3正调控SNAI 1的表达，并且敲低SNAI 1减弱SCLC细胞的迁移和侵袭能力。此外，在小鼠模型中，上调的DLL 3表达诱导皮下肿瘤生长。这些结果表明，DLL 3通过调节SNAI 1/Snail促进SCLC模型中的肿瘤生长、迁移和侵袭。
Delta-like protein 3 (DLL3) is a ligand of Notch signaling, which mediates cell-fate decisions and is tumor-suppressive or oncogenic depending on the cellular context. Previous studies show that DLL3 is highly expressed in small cell lung cancer (SCLC) but not in normal lung tissue, suggesting that DLL3 might be associated with neuroendocrine tumorigenesis. However, its role in SCLC remains unclear. To investigate the role of DLL3 in tumorigenesis in SCLC, we performed loss-of-function and gain-of-function assays using SCLC cell lines. In vitro analysis of cell migration and invasion by transwell assay showed that DLL3 knockdown reduced migration and invasion of SCLC cells, whereas DLL3 overexpression increased these activities. In addition, DLL3 positively regulated SNAI1 expression and knockdown of SNAI1 attenuated the migration and invasion ability of SCLC cells. Moreover, upregulated DLL3 expression induced subcutaneous tumor growth in mouse models. These results indicate that DLL3 promoted tumor growth, migration and invasion in an SCLC model by modulating SNAI1/Snail.