cFOS-SOX9 Axis Reprograms Bone Marrow-Derived Mesenchymal Stem Cells into Chondroblastic Osteosarcoma.
Stem Cell Reports
; 8(6): 1630-1644, 2017 06 06.
Article
en En
| MEDLINE
| ID: mdl-28552607
ABSTRACT
Bone marrow-derived mesenchymal stem cells (BMSCs) are proposed as the cells of origin of several subtypes of osteosarcoma (OS). However, signals that direct BMSCs to form different subtypes of OS are unclear. Here we show that the default tumor type from spontaneously transformed p53 knockout (p53_KO) BMSCs is osteoblastic OS. The development of this default tumor type caused by p53 loss can be overridden by various oncogenic signals RAS reprograms p53_KO BMSCs into undifferentiated sarcoma, AKT enhances osteoblastic OS, while cFOS promotes chondroblastic OS formation. We focus on studying the mechanism of cFOS-induced chondroblastic OS formation. Integrated genome-wide studies reveal a regulatory mechanism whereby cFOS binds to the promoter of a key chondroblastic transcription factor, Sox9, and induces its transcription in BMSCs. Importantly, SOX9 mediates cFOS-induced cartilage formation in chondroblastic OS. In summary, oncogenes determine tumor types derived from BMSCs, and the cFOS-SOX9 axis is critical for chondroblastic OS formation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Óseas
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Células de la Médula Ósea
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Osteosarcoma
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Proteínas Proto-Oncogénicas c-fos
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Trasplante de Células Madre Mesenquimatosas
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Factor de Transcripción SOX9
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Células Madre Mesenquimatosas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos