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Poster display session

2715 - Crucial relationship of Neural Wiskott Aldrich syndrome protein(N-WASP) and Lysyl oxidase-like 2(LOXL2) in the promotion of pancreatic cancer metastasis

Date

09 Sep 2017

Session

Poster display session

Presenters

HyungSun Kim

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

H. Kim1, J.S. Park2

Author affiliations

  • 1 Department Of Surgery, Gangnam Severance Hospital, KS013 - Seoul/KR
  • 2 Department Of Surgery, Gangnam Severance Hospital, Seoul/KR
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Resources

Abstract 2715

Background

Pancreatic cancer is known to have aggressive malignancy and poor prognosis. N-WASP is part of the WASP family that regulate actin polymerization. FAK (Focal adhesion kinase) promotes N-WASP and epithelial mesenchymal transition(EMT) in cancer metastasis. Previous studies reported the overexpression of LOXL2 activates FAK and Snail and promotes distant metastasis in pancreatic cancer. However, there are few evidence of the relation between LOXL2 and N-WASP. In this study, we aimed to confirm the expression of N-WASP and relationship of N-WASP and LOXL2 in pancreatic cancer.

Methods

Between June 2002 and December 2012, 80 patients underwent curative resection for pancreatic cancer at Gangnam Severance Hospital, Korea. Pancreatic cancer cell lines MIA PaCa-2, PANC-1 were used for in vitro study. We purified the whole RNA and protein to perform the RT-PCR and Western blot. We performed Chromatin immunoprecipitation(ChIP) assay to probe the interaction between Snail and promoter of N-WASP. And we confirmed the motility and invasiveness of MIA PaCa-2 and PANC-1.

Results

Among the 80 patients, 81.2% were positive for LOXL2. On univariate and multivariate analyses, poor differentiation and LOXL2 were identified as prognostic factors for DFS. High expression of LOXL2 and N-WASP were observed and correlated with the expression of mesenchymal markers (Snail, L1CAM, Vimentin). We generated stably LOXL2 silenced pancreatic cancer cell which exhibited significant changes of factors related to invasiveness and N-WASP expression. There were poorly expressions of N-WASP in Snail silencing of same cell lines. In ChIP assay, we obtained the results of the association of Snail proteins with promoter of N-WASP. Silencing of N-WASP decreased motility and invasiveness of MIA PaCa-2 and PANC-1 as determined from wound healing assay.

Conclusions

Our results demonstrated that N-WASP is a regulator of EMT in pancreatic cancer. By identifying of N-WASP expression promoted by Snail, LOXL2 and N-WASP have a powerful relationship for activating the promotion of EMT in pancreatic cancer metastasis. These findings suggest that N-WASP can be a target for the determining of distant metastasis in pancreatic cancer.

Clinical trial identification

Legal entity responsible for the study

Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Gangnam Severance Hospital, Yonsei University College of Medicine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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