SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling
SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling
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DOI：
10.1111/febs.13227
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发表时间：
2015-04-01
期刊：
影响因子：
5.4
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
--
作者：
Mansour, Mohammed A.;Hyodo, Toshinori;Senga, Takeshi
特异性富含AT序列结合蛋白2（SATB 2）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图案形成中具有多种作用。SATB 2与核基质附着区结合，并通过改变染色质结构来调节不同基因组的表达。最近的研究报道，SATB 2的高表达与结直肠癌和喉癌的良好预后相关;然而，SATB 2在癌细胞中是否具有肿瘤抑制功能仍不确定。在这项研究中，我们研究了SATB 2表达对结直肠癌细胞恶性特性的影响。SATB 2的表达抑制了癌细胞的体外和体内增殖，并抑制了癌细胞的迁移和侵袭。细胞外信号调节激酶5（ERK 5）是一种丝裂原活化蛋白激酶，与各种类型癌症的侵袭性表型相关。SATB 2表达降低了ERK 5的活性，ERK 5的组成性激活恢复了SATB 2表达细胞的增殖、非贴壁依赖性生长、迁移和侵袭。我们的研究结果表明，存在一种新的调节机制，SATB 2介导的肿瘤抑制通过ERK 5失活。
Special AT-rich sequence binding protein2 (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 invitro and invivo, and also suppressed their migration and invasion. Extracellular signal-regulated kinase5 (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.