RETRACTED: Down-regulation of Notch-1 inhibits invasion by inactivation of nuclear Factor-κB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. (Retracted article. See vol. 78, pg. 5476, 2018)

Notch signaling plays a critical role in the pathogenesis and progression of human malignancies but the precise role and mechanism of Notch-1 for tumor invasion remains unclear. In our earlier report, we showed that down-regulation of Notch-1 reduced nuclear factor-kappa B (NF-kappa B) DNA-binding activity and matrix metalloproteinase-9 (MMP-9) expression. Because NF-kappa B, VEGF, and MMPs are critically involved in the processes of tumor cell invasion and metastasis, we investigated the role and mechanism(s) by which Notch-1 down-regulation (using molecular approaches) may lead to the down-regulation of NF-kappa B, vascular endothelial growth factor (VEGF), and MMP-9, thereby inhibiting invasion of pancreatic cancer cells through Matrigel. We found that the down-regulation of Notch-1 by small interfering RNA decreased cell invasion, whereas Notch-1 overexpression by cDNA transfection led to increased tumor cell invasion. Consistent with these results, we found that the down-regulation of Notch-1 reduced NF-kappa B DNA-binding activity and VEGF expression. Down-regulation of Notch-1 also decreased not only MMP-9 mRNA and its protein expression but also inactivated the pro-MMP-9 protein to its active form. Taken together, we conclude that the down-regulation of Notch-1 could be an effective approach for the down-regulation and inactivation of NF-kappa B and its target genes, such as MMP-9 and VEGF expression, resulting in the inhibition of invasion and metastasis.