Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer.
EMBO J
; 31(21): 4124-39, 2012 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-23034403
ABSTRACT
Cancers and tissue stem cells (SCs) share similar molecular pathways for their self-renewal and differentiation. The race is on to identify unique pathways to specifically target the cancer, while sparing normal SCs. Here, we uncover the transcription factor Runx1/AML1, a known haematopoietic and leukaemia factor, albeit dispensable for normal adult SC homeostasis, as being important for some mouse and human epithelial cancers. We implicate Runx1 as a SC-intrinsic gene in mouse hair follicle and oral epithelia by genetic lineage tracing in adulthood. Runx1-expressing SCs, but not other cells that ectopically upregulate Runx1 by injury and inflammation, are at the skin tumour origin. Runx1 loss impairs tumour initiation and maintenance and the growth of oral, skin, and ovarian epithelial human cancer cells. Runx1 stimulates Stat3 signalling via direct transcriptional repression of SOCS3 and SOCS4 and this is essential for cancer cell growth. Thus, Runx1 is a broader epithelial SC and cancer factor than previously recognized, and qualifies as an attractive potential target for both prevention and therapy of several epithelial cancers.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Neoplasias Glandulares y Epiteliales
/
Factor de Transcripción STAT3
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Subunidad alfa 2 del Factor de Unión al Sitio Principal
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos