AI Article Synopsis
- The TGF-β signaling pathway can either promote or suppress tumors, depending on the context, particularly in breast tumor-initiating cells (BTICs).
- The interaction between SMAD3, a key component of TGF-β signaling, and the unique epigenetic modifications in BTICs influences this dual role.
- The study highlights how DNA and histone modifications alter gene accessibility, revealing that the epigenome is crucial in determining how TGF-β affects cancer cells.
Article Abstract
The transforming growth factor beta (TGF-β) signaling pathway exerts opposing effects on cancer cells, acting as either a tumor promoter or a tumor suppressor. Here, we show that these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGF-β signaling, and the distinct epigenomes of breast-tumor-initiating cells (BTICs). These effects of TGF-β are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC-suppressing contexts. Our data show cell-type-specific patterns of DNA and histone modifications provide a modulatory layer by determining accessibility of genes to regulation by TGF-β/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status and is crucial for TGF-β-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGF-β in cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695334 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2015.11.040 | DOI Listing |
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