DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling

Yu Liu; Rong Zhou; Xun Yuan; Na Han; Si Zhou; Hanxiao Xu; Mingzhou Guo; Shiying Yu; Cuntai Zhang; Tiejun Yin; Kongming Wu

doi:10.18632/oncotarget.3281

DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling

Oncotarget. 2015 Apr 20;6(11):8621-34. doi: 10.18632/oncotarget.3281.

Authors

Yu Liu¹, Rong Zhou¹, Xun Yuan², Na Han², Si Zhou¹, Hanxiao Xu², Mingzhou Guo³, Shiying Yu², Cuntai Zhang¹, Tiejun Yin¹, Kongming Wu²

Affiliations

¹ Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
² Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
³ Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, P.R. China.

Abstract

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.

Keywords: DACH1; TMA; Wnt/β-catenin signaling; hepatocellular carcinoma; prognostic factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement
Cholangiocarcinoma / metabolism
Cholangiocarcinoma / pathology
Down-Regulation
Eye Proteins / analysis
Eye Proteins / genetics
Eye Proteins / physiology*
Female
Gene Expression Regulation, Neoplastic
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Humans
Kaplan-Meier Estimate
Liver Diseases / metabolism
Liver Neoplasms / metabolism*
Liver Neoplasms / mortality
Liver Neoplasms / pathology
Male
Middle Aged
Neoplasm Proteins / analysis
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Phosphorylation
Prognosis
Protein Processing, Post-Translational
Recombinant Fusion Proteins / metabolism
Tissue Array Analysis
Transcription Factors / analysis
Transcription Factors / genetics
Transcription Factors / physiology*
Tumor Stem Cell Assay
Wnt Signaling Pathway / physiology*
beta Catenin / antagonists & inhibitors

Substances

CTNNB1 protein, human
DACH1 protein, human
Eye Proteins
Neoplasm Proteins
Recombinant Fusion Proteins
Transcription Factors
beta Catenin
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3