Tetraspanin 1 promotes epithelial-to-mesenchymal transition and metastasis of cholangiocarcinoma via PI3K/AKT signaling.
J Exp Clin Cancer Res
; 37(1): 300, 2018 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-30514341
ABSTRACT
BACKGROUND:
Numerous studies have demonstrated that tetraspanin 1 (TSPAN1), a transmembrane protein, functions as an oncoprotein in many cancer types. However, its role and underlying molecular mechanism in cholangiocarcinoma (CCA) progression remain unclear.METHODS:
In the present study, the expression of TSPAN1 in human CCA and adjacent nontumor tissues was examined using real-time PCR, western blot and immunohistochemistry. The effect of TSPAN1 on proliferation and metastasis was evaluated by functional assays both in vitro and in vivo. A luciferase reporter assay was performed to investigate the interaction between microRNA-194-5p (miR-194-5p) and TSPAN1 3'-untranslated region. Co-immunoprecipitation (co-IP) was used to confirm the interaction between TSPAN1 protein and integrin α6ß1 and western blot was used to explore TSPAN1 mechanism.RESULTS:
We found that TSPAN1 was frequently upregulated in CCA and high levels of TSPAN1 correlated with TNM stage, especially metastasis in CCA. TSPAN1 overexpression promoted CCA growth, metastasis, and induced epithelial-to-mesenchymal transition (EMT), while its silencing had the opposite effect both in vitro and in vivo. To explore the differential expression of TSPAN1, we screened miR-194-5p as the upstream regulator of TSPAN1. A combination of high-level TSPAN1 and low-level miR-194-5p predicted poor prognosis in patients with CCA. Furthermore, in accordance with the functional characteristics of the TSPAN superfamily, we proved that TSPAN1 interacted with integrin α6ß1 to amplify the phosphoinositide-3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3ß/Snail family transcriptional repressor (Snail)/phosphatase and tensin homolog (PTEN) feedback loop.CONCLUSION:
The results indicate that TSPAN1 could be a potential therapeutic target for CCA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
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Colangiocarcinoma
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
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Tetraspaninas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Exp Clin Cancer Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China