Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer.
Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer.
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TEF3-1 的核定位促进癌症中的细胞周期进展和血管生成
DOI：
10.18632/oncotarget.7342
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发表时间：
2016-03-22
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
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作者：
Teng K;Deng C;Xu J;Men Q;Lei T;Di D;Liu T;Li W;Liu X
TEF 3 -1（转录增强因子3同种型1），也称为TEAD 4（TEA结构域家族成员4），最近被揭示为癌症发展中的致癌特征。然而，潜在的分子致病机制仍不明确。本论文研究了TEF 3 -1对HUVECs G1/S期转化的促进作用，并上调细胞周期蛋白和周期蛋白依赖性激酶的表达水平。此外，如果TEF 3 -1被敲低，则细胞周期蛋白和CDKs的表达下调，而细胞周期的负调节因子P21的表达上调。微阵列分析还证实，TEF 3 -1过表达上调与细胞周期进展和促进血管生成相关的基因。此外，我们观察到核TEF 3 -1在胃癌（GC）血管结构形成过程中高度表达。最后，肿瘤异种移植实验表明，当TEF 3 -1被敲低时，肿瘤生长和血管生成也被抑制。总之，这些结果首次证明TEF 3 -1定位于细胞核刺激HUVEC中的细胞周期进程，并特异性地促进肿瘤血管生成。HUVECs中的核TEF 3 -1可能作为致癌生物标志物，并且TEF 3 -1的抑制可能是抗肿瘤治疗的潜在靶点。
TEF3-1 (transcriptional enhancer factor 3 isoform 1), also known as TEAD4 (TEA domain family member 4), was recently revealed as an oncogenic character in cancer development. However, the underlying molecular pathogenic mechanisms remain undefined. In this paper, we investigated nuclear TEF3-1 could promote G1/S transition in HUVECs, and the expression levels of cyclins and CDKs were upregulated. Additionally, if TEF3-1 was knocked down, the expression of cyclins and CDKs was downregulated while the expression of P21, a negative regulator of the cell cycle, was upregulated. A microarray analysis also confirmed that TEF3-1 overexpression upregulates genes that are related to cell cycle progression and the promotion of angiogenesis. Moreover, we observed that nuclear TEF3-1 was highly expressed during the formation of vascular structures in gastric cancer (GC). Finally, tumor xenograft experiments indicated that, when TEF3-1 was knocked down, tumor growth and angiogenesis were also suppressed. Taken together, these results demonstrate for the first time that TEF3-1 localization to the nucleus stimulates the cell cycle progression in HUVECs and specifically contributes to tumor angiogenesis. Nuclear TEF3-1 in HUVECs may serve as an oncogenic biomarker, and the suppression of TEF3-1 may be a potential target in anti-tumor therapy.