Abstract
The role of Akt3 in prostate cancer metastasis is not well understood. We investigated if Akt3 is involved in the regulation of migration and invasion of prostate cancer cells. We selected stable overexpression Akt3 clones of PC-3 androgen receptor (AR)-negative androgen-independent human prostate cancer cells. Overexpression of Akt3 suppressed cell migration and invasion as determined by the transwell and wound-healing assays. Using In Vivo Imaging System (IVIS) and Immunohistochemistry (IHC), we observed that overexpression of Akt3 suppressed cancer metastasis of PC-3 cells in nude mice orthotopic model. Western blot analysis for PC-3 cells indicated that alteration of Akt3 protein suppressed the protein abundance of epithelial-mesenchymal transition (EMT) marker protein vimentin, Snail, Ncadherin, and Slug. Meta-analysis of PubMed GEO profile data of 81 normal prostate tissues, 6 BPH tissues, 13 PIN tissues, 104 primary prostate tumors, and 51 metastatic prostate tumors indicated that Akt3 mRNA expression level was lower in metastatic prostate tumors as compared to primary prostate tumors. These observations suggested that overexpressed Akt3 regulates the migration and invasion of prostate cancer cells via adjustment of protein abundance and subcellular distribution of certain EMT marker proteins. Targeting Akt3 may be a potential treatment for prostate cancer metastases.