Introduction : Pancreatic cancer is known to have aggressive malignancy and the high rate of recurrence. During the metastasis, Multiprotein complexes including the Neural Wiskott-Aldrich Syndrome Protein(N-WASP) control dynamic remodeling of the cytoskeleton and membrane. We previously revealed that the role of LOXL2 in Pancreatic cancer metastasis. In this study we clarified the effect of modulation between the N-WASP and LOXL2 in EMT and invadopodia then find the correlation with pancreatic cancer patients.

Methods : Between June2002 and December2012, 80 patients underwent curative resection for pancreatic cancer at our hospital. Pancreatic cancer cell lines (MIA-PaCa, PANC-1, AsPC-1, BxPC3) were used to identify the expression of N-WASP and EMT markers. To confirm N-WASP expression, Western blot and RT-PCR were used and invasiveness of cells was investigated by Wound healing assay and Transwell migration assay.

Results : Among the 80 patients, both LOXL2 and N-WASP positive group shows highest mean survival rate opposite to both negative group. At in vitro studies, high expression of N-WASP was observed in pancreatic cancer cells. Transient transfection of siN-WASP exhibited significant changes of EMT markers also the marked decrease in motility and invasiveness capacity. Moreover, knockdown of both LOXL2 and N-WASP shows significantly decreased cellular movement.

Conclusions : Our results demonstrate that N-WASP has a crucial role to pancreatic cancer cell metastasis and invadopodia activity. Also, we revealed that the both LOXL2 and N-WASP expression related to recurrence free survival and cancer EMT and invasiveness. These findings suggest N-WASP potentially can be a valuable target for the determining of distant metastasis in pancreatic cancer.