DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma as a negative regulator of Wnt/β-catenin signaling.
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.
Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Yu
Y
Liu
Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Rong
R
Zhou
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Xun
X
Yuan
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Na
N
Han
Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Si
S
Zhou
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Hanxiao
H
Xu
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, P.R. China.
Mingzhou
M
Guo
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Shiying
S
Yu
Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Cuntai
C
Zhang
Department of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Tiejun
T
Yin
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Kongming
K
Wu
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005136:Eye Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D053208:Kaplan-Meier Estimate; D008107:Liver Diseases / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014410:Tumor Stem Cell Assay; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors
C495270:CTNNB1 protein, human; C486747:DACH1 protein, human; D005136:Eye Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
DACH1; TMA; Wnt/β-catenin signaling; hepatocellular carcinoma; prognostic factor