Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of ?-catenin in cancer stem-like cells.

ABSTRACT: 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, ?-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 ?-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 ?-catenin destruction complex, sequentially reduced the phosphorylation of ?-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 ?-catenin. In addition, CDC20 combined with CD44 or ?-catenin can serve as an important indicator for prognosis of patients with prostate cancer.

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC6491421 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature