Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages.
Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. ... CBP interacts with Snail and acetylates Snail at lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.
Mesh Terms:
Acetylation, Animals, Macrophages, Mice, Mice, SCID, Molecular Sequence Data, Neoplasms, Prognosis, Transcription Factors
Acetylation, Animals, Macrophages, Mice, Mice, SCID, Molecular Sequence Data, Neoplasms, Prognosis, Transcription Factors
Cancer Cell
Date: Oct. 13, 2014
PubMed ID: 25314079
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