Slug, a member of the Snail family of transcription factors, has a crucial role 
in the regulation of epithelial-mesenchymal transition (EMT) by suppressing 
several epithelial markers and adhesion molecules, including E-cadherin. A 
recent study demonstrated that no relationship exists between Slug and 
E-cadherin in pancreatic cancer. Another study showed that in malignant 
mesothelioma effusions Slug was associated with matrix metalloproteinase (MMP) 
expression, but that there was no association with E-cadherin. F-ascin is an 
actin-bundling protein involved in filopodia assembly and cancer invasion and 
metastasis of multiple epithelial cancer types. In this study, we investigated 
Slug, E-cadherin, and MMP-9 expression using immunohistochemistry in 60 patients 
with pancreatic cancer and their correlation with carcinoma invasion and 
metastasis. Additionally, we observed the effects of Slug on invasion and 
metastasis in the pancreatic cancer cell line PANC-1. Alterations in Slug, 
MMP-9, and E-cadherin were determined by RT-PCR, western blot, and 
immunohistochemistry. Alterations in MMP-9 and F-actin cytoskeleton were 
determined by immunofluorescence staining, flow cytometry (FCM), or gelatin 
zymography. Slug, E-cadherin, and MMP-9 expression in pancreatic cancer was 
significantly associated with lymph node metastases and we found a significant 
correlation between Slug and MMP-9 expression; however, no significant 
correlation was observed between Slug and E-cadherin expression. Slug 
transfection significantly increased invasion and metastasis in PANC-1 cells and 
orthotopic tumor of mouse in vivo, and significantly upregulated and activated 
MMP-9; however, there was no effect on E-cadherin expression. Slug promoted the 
formation of lamelliopodia or filopodia in PANC-1 cells. The intracellular 
F-actin and MMP-9 was increased and relocated to the front of the extending 
pseudopodia from the perinuclear pool in Slug-transfected PANC-1 cells. These 
results suggest that Slug promotes migration and invasion of PANC-1 cells, which 
may correlate with the reorganization of MMP-9 and remodeling of the F-actin 
cytoskeleton, but not with E-cadherin expression.