AID-induced CXCL12 upregulation enhances castration-resistant prostate cancer cell metastasis by stabilizing β-catenin expression

Prostate cancer (PCa) is one of the most common malignant diseases of urinary system and has poor prognosis after progression to castration-resistant prostate cancer (CRPC), and increased cytosine methylation heterogeneity is associated with the more aggressive phenotype of PCa cell line. Activation-induced cytidine deaminase (AID) is a multifunctional enzyme and contributes to antibody diversification. However, the dysregulation of AID participates in the progression of multiple diseases and related with certain oncogenes through demethylation. Nevertheless, the role of AID in PCa remains elusive. We observed a significant upregulation of AID expression in PCa samples, which exhibited a negative correlation with E-cadherin expression. Furthermore, AID expression is remarkably higher in CRPC cells than that in HSPC cells, and AID induced the demethylation of CXCL12, which is required to stabilize the Wnt signaling pathway executor β-catenin and EMT procedure. Our study suggests that AID drives CRPC metastasis by demethylation and can be a potential therapeutic target for CRPC. [Display omitted] •AID is aberrantly expressed in prostate cancer tissue and related with ISUP level•AID is highly expressed in CRPC cells and upregulates CXCL12 by demethylation•CXCL12 stabilizing the expression of β-catenin by downregulating CK1α•AID upregulates MMP14 and WLS to facilitate prostate cancer cell metastasis Natural sciences; Biological sciences; Systems biology; Cancer systems biology