PDF(Pubmed)
Abstract：
BACKGROUND: Breast cancer is one of the most common malignant tumors in women. Cell division cycle associated 5 (CDCA5), a master regulator of sister chromatid cohesion, was reported to be upregulated in several types of cancer. Here, the function and regulation mechanism of CDCA5 in breast cancer were explored.
METHODS: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms.
RESULTS: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/β-catenin signaling pathway was required for CDCA5 induced progression of breast cancer.
CONCLUSIONS: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment.
METHODS: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms.
RESULTS: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/β-catenin signaling pathway was required for CDCA5 induced progression of breast cancer.
CONCLUSIONS: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment.
摘要：
背景：乳腺癌是女性最常见的恶性肿瘤之一。细胞分裂周期相关5（CDCA5），姐妹染色单体内聚力的主要调节剂，据报道在几种类型的癌症中上调。这里,探讨CDCA5在乳腺癌中的作用及调控机制。
方法：通过免疫组织化学染色在乳腺癌标本中鉴定CDCA5的表达。采用组织芯片技术分析CDCA5表达与乳腺癌患者临床病理特征及预后的相关性。在CDCA5过表达/敲低的细胞和小鼠模型中探索了CDCA5在乳腺癌中的功能。共同IP,进行ChIP和双荧光素酶报告基因测定以阐明潜在的分子机制。
结果：我们发现CDCA5在乳腺癌组织和细胞系中的表达水平更高，CDCA5的过度表达与乳腺癌患者的不良预后显著相关。此外，CDCA5敲低显著抑制增殖和迁移,同时在体外促进细胞凋亡。机械上,我们发现CDCA5在促进E2F转录因子1（E2F1）与叉头框M1（FOXM1）启动子的结合中起重要作用。此外，体外和体内数据显示FOXM1的消耗减轻了CDCA5过表达对乳腺癌的影响。此外,我们发现Wnt/β-catenin信号通路是CDCA5诱导乳腺癌进展所必需的.
结论：我们建议CDCA5通过CDCA5/FOXM1/Wnt轴促进乳腺癌的进展，CDCA5可能成为乳腺癌治疗的新靶点。
方法：通过免疫组织化学染色在乳腺癌标本中鉴定CDCA5的表达。采用组织芯片技术分析CDCA5表达与乳腺癌患者临床病理特征及预后的相关性。在CDCA5过表达/敲低的细胞和小鼠模型中探索了CDCA5在乳腺癌中的功能。共同IP,进行ChIP和双荧光素酶报告基因测定以阐明潜在的分子机制。
结果：我们发现CDCA5在乳腺癌组织和细胞系中的表达水平更高，CDCA5的过度表达与乳腺癌患者的不良预后显著相关。此外，CDCA5敲低显著抑制增殖和迁移,同时在体外促进细胞凋亡。机械上,我们发现CDCA5在促进E2F转录因子1（E2F1）与叉头框M1（FOXM1）启动子的结合中起重要作用。此外，体外和体内数据显示FOXM1的消耗减轻了CDCA5过表达对乳腺癌的影响。此外,我们发现Wnt/β-catenin信号通路是CDCA5诱导乳腺癌进展所必需的.
结论：我们建议CDCA5通过CDCA5/FOXM1/Wnt轴促进乳腺癌的进展，CDCA5可能成为乳腺癌治疗的新靶点。
