Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cellsResearch in context
Qin Zhang,
Hai Huang,
Ao Liu,
Jiang Li,
Chunying Liu,
Bin Sun,
Lu Chen,
Yi Gao,
Danfeng Xu,
Changqing Su
Affiliations
Qin Zhang
Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China
Hai Huang
Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China
Ao Liu
Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China
Jiang Li
Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China
Chunying Liu
Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China
Bin Sun
Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China
Lu Chen
Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China; Corresponding author at: Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No 197 Ruijin Second Road, Shanghai 200025, China.
Yi Gao
Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China; Corresponding author at: Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No 197 Ruijin Second Road, Shanghai 200025, China.
Danfeng Xu
Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China; Corresponding author at: Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No 197 Ruijin Second Road, Shanghai 200025, China.
Changqing Su
Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China; Corresponding author at: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China.
Background: Cell division cycle 20 (CDC20) is frequently overexpressed in malignant tumours and involved in the differentiation process of hematopoietic stem cells. However, the role of CDC20 in prostate cancer stem-like cells (CSCs) remains poorly understood. Methods: The expression of CDC20, CD44, β-catenin were examined in prostate cancer specimens by immunohistochemistry assay, the role of CDC20 on the stem-like properties of prostate CSCs was accessed by real-time quantitive PCR, spheroid formation, in vitro and in vivo limiting dilution assay. Finding: CDC20 was associated with malignant progression of prostate cancer, the patients with both high expression CDC20 and CD44 or β-catenin were associated with more aggressive clinicopathological features and poor prognosis. CDC20 was usually enriched in CD44+ prostate CSCs. Knockdown of CDC20 could inhibit the expression of stemness-related genes, self-renewal ability, chemo-resistance, invasion capability and tumorigenicity of CD44+ prostate CSCs. Mechanistically, CDC20 promoted degradation of Axin1, the core member of β-catenin destruction complex, sequentially reduced the phosphorylation of β-catenin, promoting the latter into the nucleus, thereby enhancing the self-renewal capacity of CD44+ prostate CSCs. Interpretation: Our results indicated that CDC20 maintains the self-renewal ability of CD44+ prostate CSCs by promoting nuclear translocation and trans-activation of β-catenin. In addition, CDC20 combined with CD44 or β-catenin can serve as an important indicator for prognosis of patients with prostate cancer. Keywords: Prostate cancer, CDC20, Cancer stem like cell, β-catenin, Disease progression
