Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer
Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer
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DOI：
10.1186/s12935-019-0986-8
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发表时间：
2019-10-11
影响因子：
5.8
通讯作者：
Liu, Xiaolong
中科院分区：
文献类型：
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作者：
Sun, Jingbo;Huang, Jingzhan;Liu, Xiaolong
着丝粒蛋白F （CENPF）与着丝粒-着丝粒复合物相关，影响多种癌症的细胞增殖和转移。CENPF在乳腺癌（BC）骨转移中的作用尚不清楚。方法利用ONCOMINE数据库，比较CENPF在乳腺癌和正常组织中的表达。通过免疫组化（IHC）染色证实了60例BC患者的发现。使用GEO和Kaplan-Meier图的微阵列数据分析总生存期（OS）和无复发生存期（RFS）。利用GEO数据库，我们比较了CENPF在原发性病变、肺转移病变和骨转移病变中的表达，并在BALB/C小鼠4T1 BC模型中验证了我们的发现。基于基因集富集分析（GSEA）和western blot，我们预测了CENPF调控BC骨转移的机制。结果ONCOMINE数据库和免疫组化（IHC）显示，与正常组织相比，BC组织中CENPF的表达更高。Kaplan-Meier图还显示，高CENPF mRNA表达与较差的生存期和较短的无进展生存期（RFS）相关。从BALB/C小鼠4T1 BC模型和GEO数据库中，CENPF在原发病变、其他靶器官和骨转移中过表达。基于基因集富集分析（GSEA）和western blot，我们预测CENPF通过激活PI3K-AKT-mTORC1的能力调节甲状旁腺激素相关肽（PTHrP）的分泌。结论CENPF通过激活PI3K-AKT-mTORC1信号通路促进BC骨转移，是治疗BC的新靶点。
Background Centromere Protein F (CENPF) associates with the centromere-kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan-Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan-Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K-AKT-mTORC1. Conclusion CENPF promotes BC bone metastasis by activating PI3K-AKT-mTORC1 signaling and represents a novel therapeutic target for BC treatment.