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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Upregulation of Wnt5a promotes epithelial-to-mesenchymal transition and metastasis of pancreatic cancer cells

Authors: Haiji Bo, Shuhui Zhang, Li Gao, Ying Chen, Jing Zhang, Xuejiao Chang, Minghua Zhu

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Pancreatic cancer is one of the most lethal cancers worldwide. The aim of this study was to determine the expression pattern, clinical significance, and biological functions of Wnt5a in pancreatic cancer.

Methods

Immunohistochemistry was performed to examine Wnt5a expression in 134 surgically resected pancreatic adenocarcinoma and adjacent normal pancreatic tissues. Associations of Wnt5a expression with clinicopathological factors and cancer-specific survival were analyzed. The effects of Wnt5a overexpression or silencing on the invasiveness and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells were studied. Silencing of β-catenin by small interfering RNA was done to determine its role in the Wnt5a-mediated tumor phenotype.

Results

The percentage of Wnt5a positive expression showed a bell-shaped pattern in pancreatic cancer tissues, peaking in well-differentiated carcinomas. The median cancer-specific survival was comparable between patients with positive versus negative expression of Wnt5a. Overexpression of Wnt5a promoted the migration and invasion of pancreatic cancer cells, whereas Wnt5a depletion had an inhibitory effect. In an orthotopic pancreatic cancer mouse model, Wnt5a overexpression resulted in increased invasiveness and metastasis, coupled with induction of EMT in tumor cells. Treatment with recombinant Wnt5a elevated the nuclear β-catenin level in pancreatic cancer cells, without altering the Ror2 expression. Targeted reduction of β-catenin antagonized exogenous Wnt5a-induced EMT and invasiveness in pancreatic cancer cells.

Conclusion

Upregulation of Wnt5a promotes EMT and metastasis in pancreatic cancer models, which involves activation of β-catenin-dependent canonical Wnt signaling. These findings warrant further investigation of the clinical relevance of Wnt5 upregulation in pancreatic cancer.
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Metadata
Title
Upregulation of Wnt5a promotes epithelial-to-mesenchymal transition and metastasis of pancreatic cancer cells
Authors
Haiji Bo
Shuhui Zhang
Li Gao
Ying Chen
Jing Zhang
Xuejiao Chang
Minghua Zhu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-496

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