TES inhibits colorectal cancer progression through activation of p38.

TES inhibits colorectal cancer progression through activation of p38.
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TES 通过激活 p38 抑制结直肠癌的进展。

DOI:
10.18632/oncotarget.9961
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发表时间:
2016-07-19
期刊:
影响因子:
--
通讯作者:
Wang J
Wang J
中科院分区:
其他
文献类型:
--
作者:
Li H;Huang K;Gao L;Wang L;Niu Y;Liu H;Wang Z;Wang L;Wang G;Wang J

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人类蛋白(Testin,TES)基因已被确定为候选肿瘤抑制基因,因为它位于一个常见的脆性部位--在许多类型的肿瘤中发现了杂合性缺失的区域。为了研究它在结直肠癌(CRC)中的作用,我们检测了结直肠癌组织样本和细胞系中TES蛋白水平。我们观察到结直肠癌组织和细胞系的TES均显著降低。此外,TES的过表达显著抑制了结肠癌细胞的增殖、迁移和侵袭,同时增加了细胞的凋亡。相比之下,shRNA介导的TES基因敲除则产生了相反的效果。TES通过上调促凋亡蛋白、下调抗凋亡蛋白、同时激活p38丝裂原活化蛋白激酶(MAPK)信号通路来抑制结直肠癌的进展。总而言之,这些数据表明,TES通过激活p38-MAPK信号通路,发挥了CRC进展的必要抑制作用。提示TES在结直肠癌的诊断和靶向基因治疗方面有潜在的应用前景。
The human TESTIN (TES) gene has been identified as a candidate tumor suppressor based on its location at a common fragile site – a region where loss of heterozygosity has been detected in numerous types of tumors. To investigate its role in colorectal cancer (CRC), we examined TES protein levels in CRC tissue samples and cell lines. We observed that TES was markedly reduced in both CRC tissue and cell lines. Additionally, overexpression of TES significantly inhibited cell proliferation, migration, and invasion, while increasing cell apoptosis in colon cancer cells. By contrast, shRNA-mediated TES knockdown elicited the opposite effects. TES inhibited the progression of CRC by up-regulating pro-apoptotic proteins, down-regulating anti-apoptotic proteins, and simultaneously activating p38 mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, these data indicate that TES functions as a necessary suppressor of CRC progression by activating p38-MAPK signaling pathways. This suggests that TES may have a potential application in CRC diagnosis and targeted gene therapy.
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