TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.
TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.
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TAZ通过在神经母细胞瘤细胞中结缔组织生长因子表达的上调促进上皮过渡。
DOI：
10.3892/mmr.2014.2818
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发表时间：
2015-02
影响因子：
3.4
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Wang Q;Xu Z;An Q;Jiang D;Wang L;Liang B;Li Z
神经母细胞瘤（NB）是一种神经内分泌癌，最常见于婴儿和幼儿。Hippo信号通路调节细胞增殖和凋亡，其主要下游效应物是TAZ和yes相关蛋白1（雅普）。TAZ对神经母细胞瘤转移进展的影响及其相关机制尚不清楚。在本研究中，通过蛋白质印迹分析确定SK-N-BE（2）人神经母细胞瘤细胞的迁移和侵袭特性与TAZ的高表达水平相关。通过Transwell迁移和侵袭测定，显示SK-N-BE（2）细胞中TAZ的抑制表达导致细胞系的侵袭性降低。相反，在SK-N-SH人神经母细胞瘤细胞中TAZ的过表达通过Transwell迁移和侵袭测定以及蛋白质印迹分析显示，导致上皮-间充质转化（EMT）和侵袭性增加。Western blot和染色质免疫沉淀分析结果表明，TAZ过表达可上调CTGF的表达，而TAZ敲减可下调CTGF的表达;荧光素酶分析结果表明，TAZ通过激活TGF-β/Smad 3信号通路诱导CTGF的表达。总之，据我们所知，本研究首次证明了TAZ的过表达诱导EMT，增加了神经母细胞瘤细胞的侵袭能力。这表明，TAZ可能作为一个潜在的目标，在开发新的治疗神经母细胞瘤的疗法。
Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes-associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK-N-BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK-N-BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK-N-SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial-mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF-β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.
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影响因子：
--
作者：
Jeong, Geun Ok;Shin, Sang Hun;Kim, Jae Ho
通讯作者：
Kim, Jae Ho
影响因子：
3.7
作者：
Barbieri E;De Preter K;Capasso M;Johansson P;Man TK;Chen Z;Stowers P;Tonini GP;Speleman F;Shohet JM
通讯作者：
Shohet JM
影响因子：
6.6
作者：
Benard, Jean;Raguenez, Gilda;Valteau-Couanet, Dominique
通讯作者：
Valteau-Couanet, Dominique
影响因子：
4
作者：
Sonnylal, Sonali;Xu, Shiwen;de Crombrugghe, Benoit
通讯作者：
de Crombrugghe, Benoit
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB