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Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer
Cornelia Johanna Franziska Scheitz1, Tae Seung Lee, David James McDermitt
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
The EMBO Journal
|October 5, 2012
Summary
Runx1, a gene not vital for normal stem cells, drives epithelial cancers by activating Stat3 signaling. Targeting Runx1 offers a potential strategy for cancer prevention and therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- Cancers and tissue stem cells (SCs) share self-renewal and differentiation pathways.
- Identifying cancer-specific targets that spare normal SCs is crucial.
Purpose of the Study:
- To investigate the role of transcription factor Runx1/AML1 in epithelial cancers.
- To determine if Runx1 is a potential therapeutic target for epithelial cancers.
Main Methods:
- Genetic lineage tracing in adult mice to implicate Runx1 in SC-intrinsic gene function.
- Assessing the impact of Runx1 loss on tumor initiation, maintenance, and cancer cell growth.
- Investigating Runx1's mechanism of action on Stat3 signaling.
Main Results:
- Runx1 is essential for some mouse and human epithelial cancers, acting as an SC-intrinsic gene.
- Runx1-expressing SCs, not those with upregulated Runx1 due to inflammation, initiate skin tumors.
- Runx1 loss impairs tumor growth, and Runx1 promotes cancer cell growth by repressing SOCS3/SOCS4, activating Stat3 signaling.
Conclusions:
- Runx1 is a broader epithelial SC and cancer factor than previously understood.
- Runx1 is an attractive target for the prevention and therapy of multiple epithelial cancers.
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