DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling.
DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling.
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DACH1 是肝细胞癌中一种新型预测和预后生物标志物，作为 Wnt/β-catenin 信号传导的负调节因子
DOI：
10.18632/oncotarget.3281
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发表时间：
2015-04-20
期刊：
影响因子：
--
通讯作者：
Wu K
中科院分区：
文献类型：
--
作者：
Liu Y;Zhou R;Yuan X;Han N;Zhou S;Xu H;Guo M;Yu S;Zhang C;Yin T;Wu K
细胞命运决定因子腊肠犬（DACH 1）作为一种新的抑制剂在各种肿瘤的进展。已有研究表明，DACH 1基因启动子区甲基化与肝细胞癌（HCC）中DACH 1表达降低有关，并与HCC的进展相关，但DACH 1在HCC进展中的临床意义及确切分子机制尚不清楚。在这项研究中，我们采用了公共微阵列数据分析和组织微阵列（TMAs）技术，并显示DACH 1表达减少，即使在早期阶段的肝癌，并与肿瘤的进展。值得注意的是，Kaplan-Meier分析进一步表明DACH 1可能是HCC总生存期的独立预后因素。进一步的机制研究表明，过表达DACH 1可抑制肝癌细胞的生长和迁移，其机制部分依赖于通过磷酸化GSK 3 β抑制β-catenin而使Wnt通路失活。一致的是，DACH 1的丰度与几个Wnt靶基因呈负相关。总的来说，我们的研究表明β-catenin是HCC中DACH 1的新靶点。
The cell fate determination factor Dachshund (DACH1) functions as a novel suppressor in the progression of various neoplasms. Previous study has suggested that hypermethylation of promoter region was responsible for the reduction of DACH1 expression in hepatocellular carcinoma (HCC), and associated with the progression of HCC, but the clinical significance and the exact molecular mechanisms of DACH1 in the progression of HCC remain unclear. In this study, we employed public microarray data analysis and tissue microarrays (TMAs) technologies and showed that DACH1 expression was reduced in HCC even at early stage and associated with the tumor progression. Notably, Kaplan-Meier analysis further indicated DACH1 could be an independent prognostic factor for the overall survival of HCC. Further, mechanistic studies revealed that overexpression of DACH1 inhibited the growth and migration of HCC cell line, which were dependent in part on the inactivation of Wnt pathway via phosphorylation of GSK3β to suppress β-catenin. In agreement, the abundance of DACH1 was inversely correlated with several Wnt target genes. Collectively, our study indicated β-catenin is a novel target of DACH1 in HCC.
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影响因子：
11.2
作者：
Wu K;Chen K;Wang C;Jiao X;Wang L;Zhou J;Wang J;Li Z;Addya S;Sorensen PH;Lisanti MP;Quong A;Ertel A;Pestell RG
通讯作者：
Pestell RG
影响因子：
3.7
作者：
Powe DG;Dhondalay GK;Lemetre C;Allen T;Habashy HO;Ellis IO;Rees R;Ball GR
通讯作者：
Ball GR
影响因子：
--
作者：
Chen K;Wu K;Gormley M;Ertel A;Wang J;Zhang W;Zhou J;Disante G;Li Z;Rui H;Quong AA;McMahon SB;Deng H;Lisanti MP;Wang C;Pestell RG
通讯作者：
Pestell RG
DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
影响因子：
13.5
作者：
Mishra, Lopa;Banker, Tanuj;Murray, Joseph;Byers, Stephen;Thenappan, Arun;He, Aiwu Ruth;Shetty, Kirti;Johnson, Lynt;Reddy, E. P.
通讯作者：
Reddy, E. P.