Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Biochemistry Section, Department of Chemistry, Faculty of Science, Tanta University, Egypt.
FEBS J. 2015 Apr;282(8):1394-405. doi: 10.1111/febs.13227. Epub 2015 Feb 18.
Special AT-rich sequence binding protein 2 (SATB2) is an evolutionarily conserved transcription factor that has multiple roles in neuronal development, osteoblast differentiation, and craniofacial patterning. SATB2 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 SATB2 is associated with favorable prognosis in colorectal and laryngeal cancer; however, it remains uncertain whether SATB2 has tumor-suppressive functions in cancer cells. In this study, we examined the effects of SATB2 expression on the malignant characteristics of colorectal cancer cells. Expression of SATB2 repressed the proliferation of cancer cells in vitro and in vivo, and also suppressed their migration and invasion. Extracellular signal-regulated kinase 5 (ERK5) is a mitogen-activated protein kinase that is associated with an aggressive phenotype in various types of cancer. SATB2 expression reduced the activity of ERK5, and constitutive activation of ERK5 restored the proliferation, anchorage-independent growth, migration and invasion of SATB2-expressing cells. Our results demonstrate the existence of a novel regulatory mechanism of SATB2-mediated tumor suppression via ERK5 inactivation.
特殊富含 AT 的序列结合蛋白 2（SATB2）是一种进化上保守的转录因子，在神经元发育、成骨细胞分化和颅面模式形成中具有多种作用。SATB2 结合到核基质附着区域，并通过改变染色质结构来调节不同基因簇的表达。最近的研究报道，SATB2 的高表达与结直肠癌和喉癌的预后良好相关；然而，SATB2 是否在癌细胞中具有肿瘤抑制功能仍不确定。在这项研究中，我们研究了 SATB2 表达对结直肠癌细胞恶性特征的影响。SATB2 的表达抑制了癌细胞在体外和体内的增殖，并抑制了它们的迁移和侵袭。细胞外信号调节激酶 5（ERK5）是一种丝裂原激活的蛋白激酶，与各种类型癌症的侵袭表型有关。SATB2 表达降低了 ERK5 的活性，ERK5 的组成性激活恢复了 SATB2 表达细胞的增殖、无锚定生长、迁移和侵袭。我们的结果表明，ERK5 失活介导了 SATB2 抑制肿瘤的新型调控机制。
