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Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cells
a Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Centre for Liver Cancer, Second Military Medical University, Shanghai 200438, China
b Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No.2, Shanghai 200025, China
Cancer stem like cell β-catenin
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 Patulin (CSCs) remains poorly understood. Methods: The expression of CDC20, CD44, β-catenin were examined in prostate cancer specimens by immunohis-tochemistry 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 ex-pression 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 mem-ber of β-catenin destruction complex, sequentially reduced the phosphorylation of β-catenin, promoting the lat-ter 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 pro-moting 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.
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Prostate cancer is the first most frequently diagnosed malignancies and the second leading cause of cancer-related deaths among men in developed countries . Although prostate cancer can often be cured at early stage , patients with metastasis have to go through androgen deprivation therapy (ADT)  and inevitably progress into a drug
Corresponding author at: 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 Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No 197 Ruijin Second Road, Shanghai 200025, China.
[email protected] (C. Su).
1 These authors contributed equally to the study.
resistance stage called castration-resistant prostate cancer (CRPC), lead-ing to increased cancer-related deaths . For patients with metastatic CRPC, docetaxel-based chemotherapy is recommended as one of the first-line treatments by multiple guidelines [5,6]. However, a limited survival benefit has been proven due to the chemo-resistance and re-lapse of prostate cancer, the mechanism underlying the resistance to docetaxel for metastatic CRPC, therefore, remains obscure.
Increasing evidence has revealed that the critical role of cancer stem-like cells (CSCs) in chemo-resistance and relapse of prostate cancer [7,8]. The hypothesis of CSC suggests that tumours are maintained in the hierarchical tissues of cells, and that cancer stem cell-like cell sub-sets are essential for initiating and maintaining tumour growth due to their strong self-renewal capacity . The presence of CSC was first identified in myeloid leukemia  and has recently been observed in various solid malignancies . Concrete evidence indicated the impor-tance of prostate CSCs in tumorigenesis and anticancer drug resistance . Previous studies identified several cell surface antigens to charac-terize prostate CSCs, such as CD44 [13–17], CD133  and OV6 .