Volume 7, Issue 11 pp. 5567-5576
ORIGINAL RESEARCH
Open Access

Vasohibin 2 promotes malignant behaviors of pancreatic cancer cells by inducing epithelial-mesenchymal transition via Hedgehog signaling pathway

Ye Zhang

Ye Zhang

Wuxi People's Hospital, Nanjing Medical University, Wuxi, China

The Hormel Institute, University of Minnesota, Austin, Minnesota

College of Clinical Medicine, Nanjing Medical University, Nanjing, China

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Xiaofeng Xue

Xiaofeng Xue

First Affiliated Hospital of Suzhou University, Suzhou University, Suzhou, China

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Xiaoqian Zhao

Xiaoqian Zhao

College of Clinical Medicine, Nanjing Medical University, Nanjing, China

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Lei Qin

Lei Qin

First Affiliated Hospital of Suzhou University, Suzhou University, Suzhou, China

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Yu Shen

Yu Shen

First Affiliated Hospital of Suzhou University, Suzhou University, Suzhou, China

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Huiqiang Dou

Huiqiang Dou

Wuxi People's Hospital, Nanjing Medical University, Wuxi, China

College of Clinical Medicine, Nanjing Medical University, Nanjing, China

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Jialin Sun

Jialin Sun

College of Clinical Medicine, Nanjing Medical University, Nanjing, China

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Tong Wang

Corresponding Author

Tong Wang

Wuxi People's Hospital, Nanjing Medical University, Wuxi, China

College of Clinical Medicine, Nanjing Medical University, Nanjing, China

Correspondence

Da-Qing Yang, The Hormel Institute, University of Minnesota, Austin, Minnesota.

Email: [email protected]

and

Tong Wang, Department of General Surgery, Wuxi People's Hospital, Wuxi, Jiangsu Province, China.

Email: [email protected]

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Da-Qing Yang

Corresponding Author

Da-Qing Yang

The Hormel Institute, University of Minnesota, Austin, Minnesota

The Masonic Cancer Center, University of Minnesota, Austin, Minnesota

Correspondence

Da-Qing Yang, The Hormel Institute, University of Minnesota, Austin, Minnesota.

Email: [email protected]

and

Tong Wang, Department of General Surgery, Wuxi People's Hospital, Wuxi, Jiangsu Province, China.

Email: [email protected]

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First published: 14 October 2018
Citations: 13
Ye Zhang and Xiaofeng Xue contributed equally to this study.

Abstract

Background

Based on previous findings, we hypothesized that Vasohibin 2 (VASH2) protein may induce epithelial-mesenchymal transition (EMT) of pancreatic cancer (PC) cells by promoting the malignant behaviors of these cells. The present study aimed to test this hypothesis and explore the possible mechanisms involved.

Methods

The expression of VASH2 in PC tissues and cell lines was detected by quantitative real-time PCR and Western blot. PC cells with overexpression or knockdown of VASH2 were used to examine the involvement of VASH2 in EMT by detecting the expression of epithelial (E-cadherin) and mesenchymal (vimentin) markers and EMT-related transcription factor ZEB1/2, in gemcitabine resistance and tumor cell invasion by apoptosis and invasion assays, and in cancer stem cell-like phenotypes by detecting the proportion of CD24+CD44+ and side population (SP) cells in PC cells with flow cytometry. The impact of VASH2 overexpression and knockdown on components of the Hedgehog signaling pathway was also assessed.

Results

We found that VASH2 was highly expressed in PC tissues and cells. It promoted the EMT of PC cells by altering ZEB1/2 expression. VASH2 also stimulated invasion and chemotherapeutic resistance of PC cells and increased the proportion of cancer stem-like cells in PC cells. VASH2 did so by upregulating the expression of multiple molecules in the Hedgehog signaling pathway of PC cells.

Conclusion

VASH2 promotes malignant behaviors of PC cells by inducing EMT via activation of the Hedgehog signaling pathway.

CONFLICT OF INTEREST

None declared.

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