title: Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages.
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.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Dennis Shin-Shian
authors.initials: DS
authors.lastname: Hsu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Hsiao-Jung
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors.forename: Shyh-Kuan
authors.initials: SK
authors.lastname: Tai
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Po-Hsien
authors.initials: PH
authors.lastname: Chiu
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan; Immunity and Inflammation Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Nien-Jung
authors.initials: NJ
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
mesh_terms: D000107:Acetylation; D000818:Animals; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors