Vasohibin 2 promotes malignant behaviors of pancreatic cancer cells by inducing epithelial-mesenchymal transition via Hedgehog signaling pathway.
Cancer Med
; 7(11): 5567-5576, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30318866
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Transdução de Sinais
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Carcinoma Ductal Pancreático
/
Proteínas Angiogênicas
Limite:
Humans
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China