PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
22
06
2019
accepted:
15
11
2019
revised:
24
01
2020
pubmed:
28
12
2019
medline:
7
3
2020
entrez:
28
12
2019
Statut:
epublish
Résumé
Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.
Identifiants
pubmed: 31881074
doi: 10.1371/journal.ppat.1008221
pii: PPATHOGENS-D-19-01131
pmc: PMC6980685
doi:
Substances chimiques
Receptor, Platelet-Derived Growth Factor alpha
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008221Subventions
Organisme : NCI NIH HHS
ID : R01 CA136387
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA221208
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI073961
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA240139
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA214091
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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