Metastasis-associated protein 2 regulates human hepatocellular carcinoma metastasis progression through modulating p38MAPK/MMP2 pathways.
Hepatocellular carcinoma cell
Invasion
MMP-2
MTA2
Migration
p38MAPK
Journal
Journal of Cancer
ISSN: 1837-9664
Titre abrégé: J Cancer
Pays: Australia
ID NLM: 101535920
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
04
2019
accepted:
31
08
2019
entrez:
29
11
2019
pubmed:
30
11
2019
medline:
30
11
2019
Statut:
epublish
Résumé
Studies have shown the overexpression of metastasis-associated protein 2 (MTA2) to be associated with hepatocellular carcinoma (HCC) progression. However, the molecular mechanism of MTA2 expression in HCC is unclear. In our study, we found a higher level of MTA2 in HCC tissues than in normal tissues and a significant correlation between tumor grade and overall survival of HCC patients. We also found that MTA2 inhibition reduced the migration and invasion capabilities of HCC cells, independent of cell proliferation. Mechanistic studies have suggested that MTA2 protein and mRNA are more highly expressed in SK-Hep-1 and Huh-7 cells compared with other HCC cells. MTA2 silencing drastically reduced migration and invasion capability and also inhibited matrix metalloproteinase 2 (MMP2) at the transcriptional and translation levels in both cells. In addition, treatment with the MMP2 antibody markedly impaired MTA2-knockdown-mediated inhibition of migration and invasion in SK-Hep-1 cells. Furthermore, MTA2 knockdown reduced the phosphorylation of the p38MAPK protein, whereas the inhibition of p38MAPK (SB203580 or si-p38) confirmed that blocking the p38MAPK pathway mediated MTA2-knockdown-inhibited migration and invasion in SK-Hep-1 cells. We demonstrated the molecular mechanism by which MTA2 inhibits human HCC cell metastasis through the p38MAPK/MMP2 pathways, which might be helpful in determining the diagnostic value of this protein in patients with HCC.
Identifiants
pubmed: 31777601
doi: 10.7150/jca.35626
pii: jcav10p6716
pmc: PMC6856896
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6716-6725Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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