PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway.

Shi Yuan Wen; Yan Tong Liu; Bing Yan Wei; Jie Qiong MA; Yan Yan Chen

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PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway.

Author: Shi Yuan WEN ¹ ; Yan Tong LIU ² ; Bing Yan WEI ³ ; Jie Qiong MA ¹ ; Yan Yan CHEN ⁴
Author Information

1. College of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030000, Shanxi, China.
2. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
3. Shanxi Key Laboratory of Experimental Animals and Animal Models for Human Diseases, Laboratory Animal Center, Shanxi Medical University, Taiyuan 030000, Shanxi, China.
4. School of Medicine, Jiangsu University, Zhenjiang 212001, Jiangsu, China.
Publication Type:Journal Article
Keywords: Hepatocellular carcinoma; Metastasis; PDCD6; Proliferation
MeSH: Humans; Carcinoma, Hepatocellular/pathology*; Liver Neoplasms/pathology*; Proto-Oncogene Proteins c-akt/metabolism*; beta Catenin/metabolism*; Phosphatidylinositol 3-Kinases/metabolism*; Glycogen Synthase Kinase 3 beta/metabolism*; Cell Line; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Calcium-Binding Proteins/metabolism*; Apoptosis Regulatory Proteins/genetics*
From: Biomedical and Environmental Sciences 2023;36(3):241-252
CountryChina
Language:English
Abstract: OBJECTIVE:Programmed cell death 6 (PDCD6), a Ca ²⁺-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs).
METHODS:The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.
RESULTS:The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.
CONCLUSION:PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.