CD147 promotes epithelial‑mesenchymal transition of prostate cancer cells via the Wnt/β‑catenin pathway

Abstract

The majority of deaths among patients with prostate cancer (PCa) occur following metastasis; therefore, there is a critical need for effective treatment of metastatic PCa. Epithelial-mesenchymal transition (EMT) is vital in the early stage of cancer cell metastasis and CD147 has been reported to be associated with various types of cancer. The goal of this study was to investigate the role of CD147 in the EMT of PCa cells via short hairpin (sh)RNA-mediated knockdown of CD147 in lymph node carcinoma of the prostate (LNCaP) cells. Reverse transcription-quantitative PCR and western blotting were performed to examine gene and protein expression. Cell migration and invasion were detected using a Transwell assay. Cell Counting Kit-8 assay was performed to investigate cell viability. The knockdown of CD147 in LNCaP cells (LNCaP/shCD147 cells) resulted in an increase in the expression of E-cadherin (an epithelial marker), and a decrease in the expression of N-cadherin and vimentin (mesenchymal markers). Importantly, the downregulation of CD147 in LNCaP cells inhibited the expression levels of nuclear β-catenin and Snail, and phosphorylation of glycogen synthase kinase (GSK)-3β on Ser 9, and increased the expression of phosphorylated (p)-β-catenin (Ser33/37/Thr41). Treatment with lithium chloride (LiCl), a Wnt/β-catenin pathway agonist or a GSK-3β inhibitor, attenuated CD147 downregulation-induced p-β-catenin (Ser33/37/Thr41) expression, which resulted in the upregulation of β-catenin in the nucleus. LiCl treatment prompted β-catenin-mediated expression of target proteins such as Snail and vimentin in LNCaP/shCD147 cells, and prevented E-cadherin expression, a molecule downstream to Snail. In conclusion, these findings revealed an important role of CD147 in the regulation of the invasive and metastatic potential of PCa cells. CD147, via modulation of the Wnt/β-catenin pathway, may be implicated in the regulation of EMT of PCa cells and could be a potential therapeutic target for PCa.