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Cancer Cell. 2014 Oct 13;26(4):534-48. doi: 10.1016/j.ccell.2014.09.002.

Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages.

Author information

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
2
Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
3
Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
4
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan; Immunity and Inflammation Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
5
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan; Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 11221, Taiwan; Genome Research Center, National Yang-Ming University, Taipei 11221, Taiwan; Immunity and Inflammation Research Center, National Yang-Ming University, Taipei 11221, Taiwan; Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan. Electronic address: mhyang2@vghtpe.gov.tw.

Abstract

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.

PMID:
25314079
DOI:
10.1016/j.ccell.2014.09.002
[Indexed for MEDLINE]
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