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首页> 外文期刊>EBioMedicine >Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cells
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Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cells

机译：细胞分裂周期20（CDC20）通过稳定癌干样细胞中β-catenin推动前列腺癌的发展

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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 CD44sup+/sup prostate CSCs. Knockdown of CDC20 could inhibit the expression of stemness-related genes, self-renewal ability, chemo-resistance, invasion capability and tumorigenicity of CD44sup+/sup 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 CD44sup+/sup prostate CSCs. Interpretation Our results indicated that CDC20 maintains the self-renewal ability of CD44sup+/sup 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.
机译：背景细胞分裂周期20（CDC20）在恶性肿瘤中经常过表达，并参与造血干细胞的分化过程。然而，CDC20在前列腺癌干样细胞（CSCs）中的作用仍然知之甚少。方法采用免疫组织化学方法检测前列腺癌标本中CDC20，CD44，β-catenin的表达，实时定量PCR，球体形成，体外和体外研究CDC20在前列腺癌干细胞样特性中的作用。体内有限稀释法。发现CDC20与前列腺癌的恶性进展有关，高表达CDC20和CD44或β-catenin的患者均具有更具侵略性的临床病理特征和不良预后。 CDC20通常富含CD44 + 前列腺CSC。抑制CDC20可以抑制CD44 + 前列腺CSCs的干性相关基因的表达，自我更新能力，化学抗性，侵袭能力和致瘤性。从机理上讲，CDC20促进了β-catenin破坏复合体的核心成员Axin1的降解，依次降低了β-catenin的磷酸化，促进了后者进入细胞核，从而增强了CD44 + 前列腺CSC。解释我们的结果表明CDC20通过促进β-catenin的核易位和反式激活来维持CD44 + 前列腺CSC的自我更新能力。此外，CDC20与CD44或β-catenin的结合可作为前列腺癌患者预后的重要指标。

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