title: Cytoplasmic Localization of RUNX3 via Histone Deacetylase-Mediated SRC Expression in Oxidative-Stressed Colon Cancer Cells.
abstract: Runt domain transcription factor 3 (RUNX3) is a transcription factor that functions as a tumor suppressor. RUNX3 is frequently inactivated by epigenetic silencing or its protein mislocalization (cytoplasmic localization) in many cancer types. This study investigated whether oxidative stress induces redistribution of RUNX3 from the nucleus to the cytoplasm. The cytoplasmic localization of RUNX3 was associated with oxidative stress-induced RUNX3 phosphorylation at tyrosine residues via SRC activation. Moreover, oxidative stress increased expression of histone deacetylases (HDACs). RUNX3 phosphorylation and SRC expression induced by oxidative stress were inhibited by knockdown of HDAC1, restoring the nuclear localization of RUNX3 under oxidative stress. In conclusion, these results demonstrate that HDAC1- and SRC-mediated phosphorylation of RUNX3 induced by oxidative stress is associated with the cytoplasmic localization of RUNX3 and can lead to RUNX3 inactivation and carcinogenesis. J. Cell. Physiol. 232: 1914-1921, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.affiliation: School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Yea Seong
authors.initials: YS
authors.lastname: Ryu
authors.affiliation: School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Maeng
authors.affiliation: School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D015536:Down-Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D006657:Histones; D019000:Phosphotyrosine; D019061:src-Family Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1