Inorganic pyrophosphatase, a human prostate cancer activator

Abstract

Prostate cancer (PCa) represents a common tumor in men. Inorganic pyrophosphatase (PPA1) can promote inorganic pyrophosphate (PPi) hydrolysis. However, whether PPA1 participates in castration-resistant prostate cancer (CRPC) is unclear. PPA1 expression was herein determined by immunohistochemistry along with analysis of cell behaviors by flow cytometry and CCK-8 assay. Cell invasion was measured by BD Matrigel matrix. PPA1 was found to be significantly upregulated and positively correlated with Gleason grade of PCa. PPA1 expression was significantly higher in the PC-3 and DU145 cells than LNCaP cells and Benign prostatic hyperplasia (BPH)-1 cells. Additionally, stable overexpression of AR reduced PPA1 expression, implying the important roles of PPA1 in CRPC pathogenesis. Moreover, knockdown of PPA1 inhibited cell activities and behaviors. Furthermore, silencing of PPA1 reduced the expression of cell proliferation markers Ki-67 and PCNA, cell cycle protein cyclin D1, cyclin E, c-Myc, and MMP-2/9. Moreover, it also inhibited epithelial to mesenchymal transition (EMT) by upregulating E-cadherin and ZO-1, but downregulating N-cadherin and ZEB-2. Mechanistically, silencing of PPA1 inhibited NF-κB activation through reduction of IκBα and p65 phosphorylation. Our findings provide a critical link between PPA1 and CRPC.