AID-induced CXCL12 upregulation enhances castration-resistant prostate cancer cell metastasis by stabilizing β-catenin expression
Qi Li,
Jinfeng Fan,
Zhiyan Zhou,
Zhe Ma,
Zhifei Che,
Yaoxi Wu,
Xiangli Yang,
Peiyu Liang,
Haoyong Li
Affiliations
Qi Li
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Department of Urology, TianYou Hospital affiliated to Wuhan University of Science & Technology, Wuhan, Hubei Province, China
Jinfeng Fan
Department of Urology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China
Zhiyan Zhou
Department of Urology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China
Zhe Ma
The First Hospital of Tsinghua University, Beijing, China
Zhifei Che
Department of Urology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China
Yaoxi Wu
Department of Urology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China
Xiangli Yang
Department of Urology, TianYou Hospital affiliated to Wuhan University of Science & Technology, Wuhan, Hubei Province, China; Corresponding author
Peiyu Liang
Department of Urology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China; Corresponding author
Haoyong Li
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Corresponding author
Summary: 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.