Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma.
Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma.
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Snai2 的失调与舌鳞状细胞癌的转移和不良预后相关
DOI：
10.1002/ijc.26226
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发表时间：
2012-05-15
影响因子：
6.4
通讯作者：
Zhou, Xiaofeng
中科院分区：
文献类型：
--
作者：
Wang, Cheng;Liu, Xiqiang;Huang, Hongzhang;Ma, Huibin;Cai, Weixin;Hou, Jingsong;Huang, Lei;Dai, Yang;Yu, Tianwei;Zhou, Xiaofeng
Snail锌指转录因子超家族的成员包括Snai 1和Snai 2，参与重要的生物学过程，如上皮-间质转化（EMT）。虽然Snai 1已在许多癌症中进行了研究，但我们对Snai 2及其在口腔舌鳞状细胞癌（SCCOT）中的作用的了解有限。在这项研究中，我们证实了以前的观察，Snai 2的过度表达是一个常见的事件在SCCOT。我们进一步证明Snai 2过表达与两个独立的SCCOT患者队列（总n = 129）中的淋巴结转移相关。统计分析显示Snai 2过表达与总生存率降低相关。此外，Snai 2的过度表达与E-cadherin表达减少和波形蛋白表达增强相关，表明Snai 2在EMT中的功能作用。这些观察结果在体外得到证实，其中Snai 2的敲除诱导SCCOT细胞系从间充质样形态转变为上皮样形态，并抑制细胞侵袭和迁移。相反，Snai 2的异位转染导致增强的细胞侵袭和迁移。此外，Snai 2敲低减弱了TGFβ1诱导的SCCOT细胞系中的EMT。总之，这些数据表明Snai 2在EMT和SCCOT的进展中起主要作用，并且可以作为具有转移风险的患者的治疗靶点。
The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). While Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFβ1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT, and may serve as a therapeutic target for patients at risk of metastasis.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2.6
作者：
Mayland, MK;Sessions, DG;Lenox, J
通讯作者：
Lenox, J
影响因子：
4.8
作者：
Haraguchi, Misako;Okubo, Tadashi;Ozawa, Masayuki
通讯作者：
Ozawa, Masayuki
影响因子：
8
作者：
Olmeda, D.;Montes, A.;Cano, A.
通讯作者：
Cano, A.
影响因子：
4
作者：
Joseph, Mathew J.;Dangi-Garimella, Surabbi;Munshi, Hidayatullah G.
通讯作者：
Munshi, Hidayatullah G.