ATDC promotes the growth and invasion of hepatocellular carcinoma cells by modulating GSK‐3β/Wnt/β‐catenin signalling

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.

Simulated Microgravity Alters P-Glycoprotein Efflux Function and Expression via the Wnt/β-Catenin Signaling Pathway in Rat Intestine and Brain

“…β-Catenin accumulates in the cytoplasm, enters the nucleus, and binds to transcription factor (TCF) to promote the expression of target genes, including those encoding P-gp [ 67 , 68 , 69 ]. GSK-3β phosphorylation, can also activate the Wnt/β-catenin signaling pathway [ 70 , 71 ].…”

TRIM29 is differentially expressed in colorectal cancers of different primary locations and affects survival by regulating tumor immunity based on retrospective study and bioinformatics analysis

“…TRIM29 is a number of the TRIM family that plays an important regulatory role in immune functions (26,27). Indeed, TRIM29 has been reported to act as an oncogene in many cancers, such as CRC, breast cancer, and lung cancer (28)(29)(30)(31). It has been shown to affect immune function by regulating interferon levels and ubiquitination (26,27,32).…”

Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target

“…It can similarly activate this pathway and have the same effect on HCC cells ( 124 ). Similarly, overexpression of Ataxia telangiectasia group D complementing (ATDC) and Spindle and kinetochore-associated protein 2 (SKA2) in HCC similarly promotes HCC cell proliferation and invasion by activating this pathway ( 125 , 126 ). Among the identified Wnts, Wnt7b has the ability to suppress Axin complex activity, stop β-catenin phosphorylation from being degraded, and facilitate its nuclear translocation, all of which contribute to the activation of the Wnt/β-catenin signaling pathway.…”