PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3?/?-catenin Pathway*

Objective Programmed cell death 6 (PDCD6), a Ca2+-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/GSK3 beta/beta-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/GSK3 beta/beta-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/GSK3 beta/beta-catenin signaling and might be a potential target for HCC progression.

Automated summary

This study demonstrated that PDCD6 is overexpressed in hepatocellular carcinomas (HCCs) and promotes HCC cell proliferation, migration, and invasion through the AKT/GSK3 beta/beta-catenin signaling pathway. PDCD6 may serve as a potential target for HCC progression.