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SATB 2 suppresses the progression of colorectal cancer cells via inactivation of MEK 5/ ERK 5 signaling
Author(s) -
Mansour Mohammed A.,
Hyodo Toshinori,
Ito Satoko,
Kurita Kenji,
Kokuryo Toshio,
Uehara Keisuke,
Nagino Masato,
Takahashi Masahide,
Hamaguchi Michinari,
Senga Takeshi
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13227
Subject(s) - mapk/erk pathway , kinase , transcription factor , microbiology and biotechnology , protein kinase a , cancer research , signal transduction , biology , colorectal cancer , cancer , chemistry , gene , genetics
Special AT ‐rich sequence binding protein 2 ( SATB 2) is an evolutionarily conserved transcription factor that has multiple roles in neuronal development, osteoblast differentiation, and craniofacial patterning. SATB 2 binds to the nuclear matrix attachment region, and regulates the expression of diverse sets of genes by altering chromatin structure. Recent studies have reported that high expression of SATB 2 is associated with favorable prognosis in colorectal and laryngeal cancer; however, it remains uncertain whether SATB 2 has tumor‐suppressive functions in cancer cells. In this study, we examined the effects of SATB 2 expression on the malignant characteristics of colorectal cancer cells. Expression of SATB 2 repressed the proliferation of cancer cells in vitro and in vivo , and also suppressed their migration and invasion. Extracellular signal‐regulated kinase 5 ( ERK 5) is a mitogen‐activated protein kinase that is associated with an aggressive phenotype in various types of cancer. SATB 2 expression reduced the activity of ERK 5, and constitutive activation of ERK 5 restored the proliferation, anchorage‐independent growth, migration and invasion of SATB 2‐expressing cells. Our results demonstrate the existence of a novel regulatory mechanism of SATB 2‐mediated tumor suppression via ERK 5 inactivation.