Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines

•We examine the effect of Notch1 signaling in human small cell lung carcinoma.•We study the effect of Notch1 on cell adhesion, motility and spread.•We use siRNA technology and Notch1 plasmid transfection method.•We use xenotransplantation and tail vein xenograft mouse models for in vivo study.•Notch1 promotes cell adhesion and suppresses cell motility and metastatic spread.

IntroductionNotch signaling plays a key role in a wide variety of human neoplasms, and it can be either oncogenic or anti-proliferative. Moreover, Notch function in regulating cancer is unpredictable, and its outcome is strictly context-dependent.AimTo study the role of Notch1 signaling in human small cell lung carcinoma (SCLC) and its effect on cell invasion and metastasis.Materials and methodsWe used small interfering RNA (siRNA) technology, to down-regulate the expression of Notch1 in H69AR and SBC3 SCLC cells. On the other hand, we up-regulated Notch1 in H69 and H1688 SCLC cells through transfection with venus Notch1 intracellular domain (v.NICD) plasmid. In addition, H69 cells with v.NICD were xenotransplanted into immune-compromised Rag2(−/−) Jak3(−/−) mice, for analysis of ex vivo tumor epithelial mesenchymal transition (EMT) phenotype and for detection of metastatic cancer cells in the lung tissues. Moreover, we examined the metastatic ability for H69AR and SBC3 cells transfected with siRNA against Notch1, compared to their subsequent controls, by use of tail vein xenograft mouse models.ResultsNotch1 controls cell adhesion and EMT. Overexpression of Notch1 in SCLC switched off EMT, cell motility and cell metastatic potential.ConclusionOur results demonstrate that activation of Notch1 signaling pathway may represent a new strategy for treating human SCLC.