Function of BMP4 in the Formation of Vasculogenic Mimicry in Hepatocellular Carcinoma.
Bone morphogenetic protein 4
epithelial-mesenchymal transition
hepatocellular carcinoma
stemness
vasculogenic mimicry
Journal
Journal of Cancer
ISSN: 1837-9664
Titre abrégé: J Cancer
Pays: Australia
ID NLM: 101535920
Informations de publication
Date de publication:
2020
2020
Historique:
received:
23
09
2019
accepted:
21
01
2020
entrez:
24
3
2020
pubmed:
24
3
2020
medline:
24
3
2020
Statut:
epublish
Résumé
Vasculogenic mimicry (VM) is linked to vascular invasion of human hepatocellular carcinoma (HCC). BMP4, one BMP family member, is upregulated in several cancers. The purpose of this report is to identify the function of BMP4 in the formation of VM in HCC and the mechanism underling this regulation. In our report, BMP4 up-regulation resulted in an increase in migration, invasion and channel-like structure formation as well as induced epithelial-mesenchymal transition (EMT) process and stem cell-associated proteins OCT4 and SOX2 expression in HCC cells. In addition, The VM-associated proteins, including EphA2, VE-cadherin and MMP2, also could be effectively enhanced by the overexpression of BMP4. Furthermore, according to the TCGA database, higher expression of BMP4 is seen in HCC in contrast to normal liver samples. Immunohistochemistry revealed that BMP4 was positively associated with VM formation, age, histological differentiation, HCC stage, and shorter survival duration. These data demonstrated that BMP4 could promote VM network formation in HCC through induction of stemness in EMT and modulating the EphA2/VE-cadherin/MMP2 signaling pathway.
Identifiants
pubmed: 32201526
doi: 10.7150/jca.40558
pii: jcav11p2560
pmc: PMC7066000
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2560-2571Informations 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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