Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, β-catenin and EZH2
Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, β-catenin and EZH2
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DOI：
10.1093/carcin/bgu057
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发表时间：
2014-06-01
期刊：
影响因子：
4.7
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Weng, Yu-Rong;Yu, Ya-Nan;Fang, Jing-Yuan
C9 orf 140是一个新发现的与细胞增殖和致瘤性相关的基因。C9 orf 140在人胃癌和结直肠癌（CRC）中表达上调;然而，关于其在CRC进展中的作用知之甚少。我们研究了C9 orf 140信号通路的临床意义、生物学效应和机制。我们发现，C9 orf 140的表达显着增加，在一个子集的CRC和相关的血管浸润和淋巴结转移显着。我们的发现表明，敲低C9 orf 140在体外显著降低细胞增殖和侵袭，在体内显著增加总存活率并降低肺转移。相反，与对照肿瘤相比，C9 orf 140的过表达显著增加了肺转移，缩短了总生存期。C9 orf 140诱导的大肠癌细胞侵袭可能依赖于促进上皮-间质转化进程。STAT 5可直接与zeste增强子同源物2（EZH 2）和β-连环蛋白相互作用以增强C9 orf 140基因的反式激活。此外，C9 orf 140可能参与由STAT 5、EZH 2或β-catenin激活诱导的细胞侵袭。我们描述了C9 orf 140在结直肠癌进展中的作用，发现C9 orf 140过表达可能受到STAT 5、EZH 2和β-catenin相互作用的调节。
C9orf140 is a newly identified and characterized gene which is associated with cell proliferation and tumorigenicity. Expression of C9orf140 is upregulated in human gastric cancer and colorectal cancer (CRC); however, little is known about its role in CRC progression. We have investigated the clinical significance, biological effects and mechanisms of C9orf140 signaling. We found that the expression of C9orf140 is dramatically increased in a subset of CRC and correlates significantly with vascular invasion and lymph node metastasis. Our finding showed that knockdown of C9orf140 significantly reduced cell proliferation and invasion in vitro and dramatically increased overall survival and decreased lung metastasis in vivo. Conversely, overexpression of C9orf140 significantly increased lung metastasis and shortened overall survival when compared with control tumors. C9orf140-induced CRC cell invasion may depend on promoting the epithelial-mesenchymal transition progression. STAT5 may directly interact with the enhancer of zeste homolog 2 (EZH2) and beta-catenin to enhance C9orf140 gene transactivation. Furthermore, C9orf140 may participate in cell invasion which is induced by STAT5, EZH2 or beta-catenin activation. We describe the role of C9orf140 in CRC progression and find that C9orf140 overexpression may be regulated by STAT5, EZH2 and beta-catenin interaction.