DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail

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. This study performed in vitro and in vivo analyses of the role of delta‐like protein 3 (DLL3) in small cell lung cancer (SCLC) by targeted siRNA silencing in SCLC cell lines, followed by implantation of DLL3‐overexpressing or control SCLC cells into mouse models to assess altered tumorigenesis. Our results showed that DLL3 downregulation attenuated SCLC‐cell proliferation, migration and invasion in a process involving the attenuation of Snail activation. In addition, we found that DLL3 overexpression promoted subcutaneous tumor growth in the mouse models.