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

Ye Zhang,Tong Wang,Huiqiang Dou,Yu Shen,Da‐Qing Yang,Xiaofeng Xue,Lei Qin,Jialin Sun,Xiaoqian Zhao

doi:10.1002/cam4.1752

Ye Zhang, Tong Wang + Show 7 more

Open Access

https://doi.org/10.1002/cam4.1752

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Abstract

BackgroundBased 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.MethodsThe 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.ResultsWe 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.ConclusionVASH2 promotes malignant behaviors of PC cells by inducing EMT via activation of the Hedgehog signaling pathway.

Highlights

Pancreatic cancer (PC) is the fourth leading cause of cancer death accounting for nearly 7% of all deaths in cancer patients.[1]
We discovered that Vasohibin 2 (VASH2) expression is significantly increased in pancreatic cancer (PC) tissues and cell lines
We found that VASH2 expression is significantly elevated in PC tissues and VASH2 promotes esenchymal transition (EMT) in PC cell lines, indicating that VASH2

Summary

| INTRODUCTION

Pancreatic cancer (PC) is the fourth leading cause of cancer death accounting for nearly 7% of all deaths in cancer patients.[1]. In PC, overexpression of VASH2 is associated with accelerated tumor malignant transformation and reduced chemosensitivity to gemcitabine.[13] Our study suggests that VASH2 is involved in promoting EMT of HCC cells.[14] we hypothesized that VASH2 may regulate EMT in PC cells. To test this hypothesis, we examined the role of VASH2 in the EMT and various malignant behaviors, including gemcitabine resistance, invasion, and increased cancer stem cell- like phenotypes, of PC cells.

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Findings

| DISCUSSION