Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway
Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway
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硫氧还蛋白样蛋白 2b 通过 NF-kappaB 途径促进结肠癌细胞增殖并抑制细胞凋亡。
DOI：
10.1016/j.canlet.2014.12.048
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发表时间：
2015-07-28
期刊：
影响因子：
9.7
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Lu, Yuanyuan;Zhao, Xiaodi;Fan, Daiming
本课题组前期工作发现硫氧还蛋白家族新成员硫氧还蛋白样蛋白2（Txl-2）是单克隆抗体MO的靶点，MO能高灵敏度、高特异性地检测结肠癌。在本研究中，最丰富的异构体Txl-2b在细胞增殖和凋亡中的功能进行了研究。Txl-2过表达与临床分期增加相关。Txl-2b抑制SW 620细胞增殖，诱导细胞周期停滞在G1/S期，并导致对长春新碱诱导的细胞凋亡的反应。Txl-2b在LoVo细胞中的过表达具有相反的作用，这依赖于Trx结构域功能。体内研究证实Txl-2b表达促进裸鼠结肠癌的发生。进一步的研究表明，核因子-κ B（NF-κ B）信号被Txl-2 B激活。抑制NF-κ B活化可通过降低Cyclin D1、Bcl-2、Bcl-xL和Survivin表达和增加Caspase-3活化，部分消除Txl-2 B介导的促增殖和抗凋亡表型。总体而言，我们的研究结果表明，Txl-2b的表达刺激癌细胞增殖，加速细胞周期，并有助于结肠癌的凋亡抗性，并为结肠癌治疗提供了一个潜在的治疗靶点。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Our previous work identified thioredoxin-like protein 2 (Txl-2), a novel thioredoxin family member, as the target of the monoclonal antibody MO which can detect colon cancer with high sensitivity and specificity. In the present study, the function of the most abundant isoform Txl-2b in cell proliferation and apoptosis was investigated. Txl-2 overexpression correlated with increased clinical stages. Inhibition of Txl-2b suppressed cell proliferation, induced cell cycle arrest at the G1/S phase, and led to responsiveness to the vincristine-induced apoptosis in SW620 cells. Txl-2b overexpression in LoVo cells had the opposite effect, which was dependent on Trx domain function. In vivo studies validated that Txl-2b expression promoted colon cancer tumorigenesis in nude mice. Further studies revealed that nuclear factor-kappa B (NF-kappa B) signaling was activated by Txl-2b. Inhibition of NF-kappa B activation partly abrogated the pro-proliferation and anti-apoptotic phenotypes mediated by Txl-2b via reduced Cyclin D1, Bcl-2, Bcl-xL and Survivin expression and increased Caspase-3 activation. Overall, our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.