CUEDC1 inhibits epithelial-mesenchymal transition via the TβRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.
CUEDC1 inhibits epithelial-mesenchymal transition via the TβRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.
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CUEDC1 通过 TβRI/Smad 信号通路抑制上皮间质转化，并抑制非小细胞肺癌的肿瘤进展。
DOI：
10.18632/aging.103329
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发表时间：
2020-10-25
期刊：
影响因子：
--
通讯作者：
Xing Y
中科院分区：
文献类型：
--
作者：
Cui Y;Song Y;Yan S;Cao M;Huang J;Jia D;Liu Y;Zhang S;Fan W;Cai L;Li C;Xing Y
肺癌由于其高转移潜力而仍然是全世界最致命的癌症。上皮-间质转化（EMT）是肿瘤转移的第一步，但EMT的调控机制尚不清楚。在这项研究中，我们首次发现CUEDC 1低表达与非小细胞肺癌（NSCLC）患者的淋巴结转移相关，采用免疫组织化学（IHC）。CUEDC 1基因敲减促进了NSCLC细胞的转移和EMT进程，并激活了TβRI/Smad信号通路。过表达CUEDC 1可降低肺癌细胞的转移潜能，抑制EMT过程，并使TβRI/Smad信号通路失活。免疫沉淀（IP）分析表明，Smurf 2是一种新的CUEDC 1相互作用蛋白。此外，CUEDC 1可以通过降解Smurf 2来调节Smurf 2的表达。Smurf 2过表达可阻断CUEDC 1敲低诱导的EMT和TβRI/Smad信号通路的激活，而siRNA Smurf 2可逆转CUEDC 1过表达对EMT和TβRI/Smad信号通路的调节。此外，CUEDC 1抑制NSCLC细胞的增殖并促进其凋亡。在体内，与对照细胞相比，CUEDC 1敲低细胞促进转移和肿瘤生长。总之，我们的研究结果表明CUEDC 1在NSCLC进展中的关键作用，并为其治疗方法的临床研究提供支持。
Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 expression correlated with lymph node metastasis in non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC). CUEDC1 knockdown promoted the metastasis of NSCLC cells and EMT process and activated TβRI/Smad signaling pathway. Overexpression of CUEDC1 decreased the metastatic potential of lung cancer cells and inhibited the EMT process and inactivated TβRI/Smad signaling pathway. Immunoprecipitation (IP) assays showed that Smurf2 is a novel CUEDC1-interacting protein. Furthermore, CUEDC1 could regulate Smurf2 expression through the degradation of Smurf2. Overexpression of Smurf2 abolished CUEDC1 knockdown induced-EMT and the activation of TβRI/Smad signaling pathway, while siRNA Smurf2 reversed CUEDC1 overexpression-mediated regulation of EMT and TβRI/Smad signaling pathway. Additionally, CUEDC1 inhibited proliferation and promoted apoptosis of NSCLC cells. In vivo, CUEDC1-knockdown cells promoted metastasis and tumor growth compared with control cells. In conclusion, our findings indicate that the crucial role of CUEDC1 in NSCLC progression and provide support for its clinical investigation for therapeutic approaches.
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影响因子：
9.2
作者：
Liu, Furao;Xia, Zebin;Li, Dong
通讯作者：
Li, Dong
CUEDC2通过抑制STAT3和NF-κB信号通路的激活来抑制胶质瘤致瘤性
影响因子：
5.2
作者：
Li F;Tang C;Jin D;Guan L;Wu Y;Liu X;Wu X;Wu QY;Gao D
通讯作者：
Gao D
影响因子：
3.7
作者：
Fenner BJ;Scannell M;Prehn JH
通讯作者：
Prehn JH
影响因子：
9.7
作者：
Lopes, Rui;Korkmaz, Gozde;Agami, Reuven
通讯作者：
Agami, Reuven
影响因子：
4.7
作者：
Koganti P;Levy-Cohen G;Blank M
通讯作者：
Blank M