ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1.
ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1.
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ELF3 是致癌信号传导诱导的 EMT-TF ZEB1 表达的拮抗剂
DOI：
10.1080/15384047.2018.1507256
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发表时间：
2019
影响因子：
3.6
通讯作者：
Ewing RM
中科院分区：
文献类型：
--
作者：
Liu D;Skomorovska Y;Song J;Bowler E;Harris R;Ravasz M;Bai S;Ayati M;Tamai K;Koyuturk M;Yuan X;Wang Z;Wang Y;Ewing RM
背景：上皮-间充质转化（epithelial -to-mesenchymal transition， EMT）是上皮细胞向迁移和侵袭性肿瘤细胞转化的关键步骤。复杂的正调控和负调控过程调控着EMT。许多致癌信号通路可以诱导EMT，但其发生的具体机制以及如何控制这一过程尚不完全清楚。方法：采用RNA-Seq分析、蛋白质网络计算分析和大规模癌症基因组学数据集，鉴定ELF3是EMT标志物表达的负调控因子。利用Western blotting结合siRNA以及肿瘤/正常结直肠癌组的分析来研究ELF3的表达和功能。结果：表达突变型和野生型β-catenin的结直肠癌细胞的RNA-Seq分析以及表达诱导型突变型RAS的结直肠癌细胞的分析显示，ELF3的表达在响应致癌信号通路时降低，并拮抗Wnt和RAS的致癌信号通路。肿瘤基因组图谱（Cancer Genome Atlas， TCGA）的基因表达模式分析和结直肠癌肿瘤组的蛋白定位显示，ELF3的表达与β-catenin和EMT标志物呈抗相关，与较好的临床预后相关。结论：ELF3是EMT转录因子（EMT- tf） ZEB1的负调节因子，通过其作为致癌信号拮抗剂的功能。
Background: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood. Methods: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers. Western blotting coupled to siRNA as well as analysis of tumour/normal colorectal cancer panels was used to investigate the expression and function of ELF3. Results: RNA-Seq analysis of colorectal cancer cells expressing mutant and wild-type β-catenin and analysis of colorectal cancer cells expressing inducible mutant RAS showed that ELF3 expression is reduced in response to oncogenic signalling and antagonizes Wnt and RAS oncogenic signalling pathways. Analysis of gene-expression patterns across The Cancer Genome Atlas (TCGA) and protein localization in colorectal cancer tumour panels showed that ELF3 expression is anti-correlated with β-catenin and markers of EMT and correlates with better clinical prognosis. Conclusions: ELF3 is a negative regulator of the EMT transcription factor (EMT-TF) ZEB1 through its function as an antagonist of oncogenic signalling.
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影响因子：
3.7
作者：
Roca H;Hernandez J;Weidner S;McEachin RC;Fuller D;Sud S;Schumann T;Wilkinson JE;Zaslavsky A;Li H;Maher CA;Daignault-Newton S;Healy PN;Pienta KJ
通讯作者：
Pienta KJ
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
9.7
作者：
Min KW;Lee SH;Baek SJ
通讯作者：
Baek SJ
影响因子：
11.8
作者：
Lee, Briana;Villarreal-Ponce, Alvaro;Fallahi, Magid;Ovadia, Jeremy;Sun, Peng;Yu, Qian-Chun;Ito, Seiji;Sinha, Satrajit;Nie, Qing;Dai, Xing
通讯作者：
Dai, Xing
影响因子：
5.2
作者：
Vu T;Datta PK
通讯作者：
Datta PK