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.
Highlights
Despite significant achievement has been made in early diagnosis and surgical intervention, hepatocellular carcinoma (HCC) still ranks the leading cause of cancerrelated mortality, with < 26% patients surviving beyond 5 years [1]
In order to comprehend the significance of DACH1 expression in liver benign as well as malignant lesions, we analyzed DACH1 protein levels in a tissue microarrays (TMAs) containing 120 informative patients with various hepatic lesions, which mainly included cirrhosis, steatosis, chronic hepatitis, hemangioma and cancer
This paper provided results that DACH1 was lost in HCC and associated with the tumor progression as recently published [19]
Summary
Despite significant achievement has been made in early diagnosis and surgical intervention, hepatocellular carcinoma (HCC) still ranks the leading cause of cancerrelated mortality, with < 26% patients surviving beyond 5 years [1]. As is true in most disease processes, the best chance for long time survival of HCC comes from the active surveillance of patients known to be at high risk so that they can be diagnosed and treated at early stage [2]. There are no effective clues for screening AFP negative HCC patients. It is imperative to identify the early stage HCC biomarkers to improve diagnostic methods. Identification of biomarkers could improve our understanding of cellular and molecular mechanisms engaged in the pathogenesis of HCC and provide new targets for drug development and gene therapy [4]
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