Abstract 4103: Knockdown of Notch1 inhibits tumor cell proliferation, migration, and invasion and reverses epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma

Abstract Despite a large bodies of evidences support an oncogenic role of Notch signaling in several human solid cancers, however, the pleiotropic effects and molecular mechanisms of blockage of Notch signaling on nasopharyngeal carcinoma (NPC) remain unclear. In this study, Real-time RT-PCR and western blotting were firstly used to examine the expression of Notch1 receptor in a panel of NPC cell lines. CNE1 and CNE2 cells expressed a higher level of Notch1 compared to HONE1, SUNE1 and HK cells. Then Notch1 expression was specifically knocked down in CNE1 and CNE2 cells by Notch1 short hairpin RNA (shRNA). This resulted in a significant inhibition of cell proliferation, migration, and invasion; and interestingly, epithelial-mesenchymal transition (EMT) was reversed in these Notch1-transfected cells along with demonstration of epithelialioid-like morphology change and increase of E-cadherin and decrease of Vimentin expressions. In addition, targeted knockdown of Notch1 dramatically inhibited expression of urokinase plasminogen activator (uPA) and its receptor uPAR, chemokine CCL2 and CXCL16 indicating that these factors are downstream targets of Notch1. Finally, knockdown of Notch1 significantly diminished CNE1 cell growth in a murine model concomitant with inhibition of cell proliferation and induction of apoptosis. Taken together, these results suggest Notch1 may become a therapeutic target in nasopharyngeal carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Huajiao Guo, Yi Lu, Chaonan Qian, Jian Zhang. Knockdown of Notch1 inhibits tumor cell proliferation, migration, and invasion and reverses epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4103. doi:10.1158/1538-7445.AM2015-4103