ATDC promotes the growth and invasion of hepatocellular carcinoma cells by modulating GSK‐3β/Wnt/β‐catenin signalling. (26th June 2019)

• Record Type: Journal Article
• Authors: Li, Weizhi; Xue, Hui; Li, Yingchao; Li, Peijie; Ma, Fuquan; Liu, Mengying; Kong, Shuzhen
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 46:Number 9(2019)
• Page Start: 845
• Page End: 853
• Publication Date: 2019-06-26
• Subjects: β‐catenin -- ataxia telangiectasia group D complementing -- glycogen synthase kinase‐3β -- hepatocellular carcinoma -- Wnt; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13119
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: Accumulating evidence has suggested that the ataxia telangiectasia group D complementing (ATDC) gene is an emerging cancer‐related gene in multiple human cancer types. However, little is known about the role of ATDC in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the expression level, biological function and underlying mechanism of ATDC in HCC. The expression of ATDC in HCC cells was detected by quantitative real‐time polymerase chain reaction and western blot analysis. Cell growth was determined by cell counting kit‐8 assay and colony formation assay. Cell invasion was assessed by Transwell invasion assay. The activation status of Wnt/β‐catenin signalling was evaluated by the luciferase reporter assay. Functional experiments showed that the silencing of ATDC expression significantly suppressed the growth and invasion of HCC cells, whereas the overexpression of ATDC promoted the growth and invasion of HCC cells in vitro. Moreover, we showed that ATDC overexpression promoted the phosphorylation of glycogen synthase kinase (GSK)‐3β and resulted in the activation of Wnt/β‐catenin signalling. Notably, the inhibition of GSK‐3β activity significantly abrogated the tumour suppressive effect of ATDC silencing, while the silencing of β‐catenin partially reversed the oncogenic effect of ATDC overexpression. Taken together, these findings reveal an oncogenic role of ATDC in HCC and show that the suppression of ATDC impedes the growth and invasion of HCC cells associated with the inactivation of Wnt/β‐catenin signalling. Our study suggests that ATDC may serve as a potential therapeutic target for HCC.