The Epstein-Barr Virus-Encoded EBNA1 Protein Activates the Bone Morphogenic Protein (BMP) Signalling Pathway to Promote Carcinoma Cell Migration.
Epstein-Barr nuclear antigen 1
Epstein-Barr virus
bone morphogenic protein
undifferentiated nasopharyngeal carcinoma
Journal
Pathogens (Basel, Switzerland)
ISSN: 2076-0817
Titre abrégé: Pathogens
Pays: Switzerland
ID NLM: 101596317
Informations de publication
Date de publication:
21 Jul 2020
21 Jul 2020
Historique:
received:
20
06
2020
revised:
15
07
2020
accepted:
17
07
2020
entrez:
26
7
2020
pubmed:
28
7
2020
medline:
28
7
2020
Statut:
epublish
Résumé
The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) protein is expressed in all virus-associated malignancies, where it performs an essential role in the maintenance, replication and transcription of the EBV genome. In recent years, it has become apparent that EBNA1 can also influence cellular gene transcription. Here, we demonstrate that EBNA1 is able to stimulate the expression of the Transforming growth factor-beta (TGFβ) superfamily member, bone morphogenic protein 2 (BMP2), with consequential activation of the BMP signalling pathway in carcinoma cell lines. We show that BMP pathway activation is associated with an increase in the migratory capacity of carcinoma cells, an effect that can be ablated by the BMP antagonist, Noggin. Gene expression profiling of authentic EBV-positive nasopharyngeal carcinoma (NPC) tumours revealed the consistent presence of BMP ligands, established BMP pathway effectors and putative target genes, constituting a prominent BMP "signature" in this virus-associated cancer. Our findings show that EBNA1 is the major viral-encoded protein responsible for activating the BMP signalling pathway in carcinoma cells and supports a role for this pathway in promoting cell migration and possibly, metastatic spread.
Identifiants
pubmed: 32708289
pii: pathogens9070594
doi: 10.3390/pathogens9070594
pmc: PMC7400503
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Cancer Research UK
ID : C198/A3916
Pays : United Kingdom
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