Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling.
Br J Cancer
; 123(7): 1145-1153, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32624579
ABSTRACT
BACKGROUND:
Wisteria floribunda agglutinin (WFA)+ Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.METHODS:
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of M2BP were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.RESULTS:
M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.CONCLUSIONS:
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Carcinoma Hepatocelular
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Serina-Treonina Quinases TOR
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Neoplasias Hepáticas
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Antígenos de Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão