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EMBO J. 2012 Nov 5;31(21):4124-39. doi: 10.1038/emboj.2012.270. Epub 2012 Oct 2.

Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer.

Author information

1
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.

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.

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PMID:
23034403
PMCID:
PMC3492731
DOI:
10.1038/emboj.2012.270
[Indexed for MEDLINE]
Free PMC Article

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