Dissecting the novel molecular interactions of solute carrier family 4 member 4 (SLC4A4) for prostate cancer (PCa) progression

Abstract

Abstract Prostate cancer (PCa) is the most common malignancy diagnosed in men. The purpose of this study was to report the mechanistic pathways of SLC4A4 in the progression of PCa. Here, we report our findings from clinical specimens of prostatic acinar adenocarcinoma collected from patients. We found that low grade prostate cancers have higher SLC4A4 expression compared to high grade cancers. We investigate the role of SLC4A4 and the signaling mechanism underlying its role in modulating the PCa progression. We report the SLC4A4/RB axis, which acts to drive the cell proliferation. SLC4A4 knockdown decreases the interaction between these molecules with hypophosphorylation of RB protein and cell cycle arrest. We also investigate the SLC4A4/GSK-3β/β-catenin signaling axis which regulates the clonogenic potential, invasiveness and metastasis. Functional analysis reveals that SLC4A4 knockdown retards tumor growth and lower the invasion and migration potential. This is related to relieve of the GSK-3β activity, which phosphorylates β-catenin at Ser33/37 with reduction of β-catenin level in PCa cells. Likewise, transcriptome sequencing using the SLC4A4 knockdown in DU145 shows regulation of differentiated expressed genes and multiple metabolic pathways. Our results suggest that SLC4A4 may serve as a potential therapeutic target for prostate cancer patients in the future.