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Cytoplasmic Localization of RUNX3 via Histone Deacetylase‐Mediated SRC Expression in Oxidative‐Stressed Colon Cancer Cells
Author(s) -
Kang Kyoung Ah,
Piao Mei Jing,
Ryu Yea Seong,
Maeng Young Hee,
Hyun Jin Won
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25746
Subject(s) - histone deacetylase , cytoplasm , proto oncogene tyrosine protein kinase src , cancer , cancer research , microbiology and biotechnology , hdac10 , oxidative phosphorylation , histone , colorectal cancer , hdac11 , histone deacetylase 5 , chemistry , biology , signal transduction , biochemistry , gene , genetics
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.