12-O-Tetradecanoylphorbol-13-Acetate Induces Up-Regulated Transcription of Variant 1 but Not Variant 2 of VIL2 in Esophageal Squamous Cell Carcinoma Cells via ERK1/2/AP-1/Sp1 Signaling.
12-O-Tetradecanoylphorbol-13-Acetate Induces Up-Regulated Transcription of Variant 1 but Not Variant 2 of VIL2 in Esophageal Squamous Cell Carcinoma Cells via ERK1/2/AP-1/Sp1 Signaling.
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12-O-Tetradecanoylphorbol-13-Acetate 通过 ERK1/2/AP-1/Sp1 信号转导在食管鳞状细胞癌细胞中诱导 VIL2 变体 1 转录上调，但不上调 VIL2 变体 2。
DOI：
10.1371/journal.pone.0124680
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Xu LY
中科院分区：
文献类型：
--
作者：
Zhang XD;Xie JJ;Liao LD;Long L;Xie YM;Li EM;Xu LY
膜-细胞骨架连接组织者ezrin可能是最“引人注目”的肿瘤标志物，在近三分之一的人类恶性肿瘤中强烈过度表达。然而，ezrin异常表达的分子机制仍然需要澄清。由VIL 2基因编码的Ezrin具有两种转录起始位点（TSS）不同的转录变体：V1和V2。V1和V2编码相同的蛋白质。在此，我们发现12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）诱导人VIL 2在食管鳞状细胞癌（ESCC）细胞中过表达。此外，VIL 2 V1，而不是V2上调TPA刺激后，在时间依赖性的方式。VIL 2 V1启动子区域内的AP-1和Sp1结合位点不仅作为VIL 2 V1的基础转录元件，而且作为复合TPA应答元件（TRE）参与VIL 2 V1的转录。TPA刺激通过激活ERK 1/2途径增强c-Jun和Sp1与TRE的结合，并增加c-Jun、c-Fos和Sp1的蛋白水平，导致VIL 2 V1的过度表达，而MEK 1/2抑制剂U 0126阻断了这些事件。最后，我们发现TPA促进了ESCC细胞的迁移，而MEK 1/2抑制剂或ezrin沉默可以部分逆转这种改变。总之，这些结果表明TPA能够通过激活MEK/ERK 1/2信号传导和增加Sp1和c-Jun与VIL 2 V1启动子的TRE的结合来诱导ESCC细胞中VIL 2 V1的过表达，并且VIL 2是重要的TPA诱导的效应子。
The membrane-cytoskeleton link organizer ezrin may be the most “dramatic” tumor marker, being strongly over-expressed in nearly one-third of human malignancies. However, the molecular mechanisms of aberrant ezrin expression still need to be clarified. Ezrin, encoded by the VIL2 gene, has two transcript variants that differ in the transcriptional start site (TSS): V1 and V2. Both V1 and V2 encode the same protein. Here, we found that 12-O-tetradecanoylphorbol-13-acetate (TPA) induced over-expression of human VIL2 in esophageal squamous cell carcinoma (ESCC) cells. Furthermore, VIL2 V1 but not V2 was up-regulated after TPA stimulation in a time-dependent manner. AP-1 and Sp1 binding sites within the promoter region of VIL2 V1 acted not only as basal transcriptional elements but also as a composite TPA-responsive element (TRE) for the transcription of VIL2 V1. TPA stimulation enhanced c-Jun and Sp1 binding to the TRE via activation of the ERK1/2 pathway and increased protein levels of c-Jun, c-Fos, and Sp1, resulting in over-expression of VIL2 V1, whereas the MEK1/2 inhibitor U0126 blocked these events. Finally, we showed that TPA promoted the migration of ESCC cells whereas MEK1/2 inhibitor or ezrin silencing could partially inverse this alteration. Taken together, these results suggest that TPA is able to induce VIL2 V1 over-expression in ESCC cells by activating MEK/ERK1/2 signaling and increasing binding of Sp1 and c-Jun to the TRE of the VIL2 V1 promoter, and that VIL2 is an important TPA-induced effector.
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磷酸肌醇的结合和磷酸化在ezrin的激活机理中依次起作用。
影响因子：
7.8
作者：
Fievet, BT;Gautreau, A;Roy, C;Del Maestro, L;Mangeat, P;Louvard, D;Arpin, M
通讯作者：
Arpin, M
影响因子：
3.3
作者：
LaLonde DP;Garbett D;Bretscher A
通讯作者：
Bretscher A
DOI：
10.1186/bcr1006
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Elliott BE;Meens JA;SenGupta SK;Louvard D;Arpin M
通讯作者：
Arpin M
影响因子：
--
作者：
Li, Qingchang;Gao, Hui;Wang, Enhua
通讯作者：
Wang, Enhua
影响因子：
4.8
作者：
Jang, SI;Steinert, PM
通讯作者：
Steinert, PM