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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Metastasis | Primary research

Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer

Authors: Jingbo Sun, Jingzhan Huang, Jin Lan, Kun Zhou, Yuan Gao, Zhigao Song, Yunyao Deng, Lixin Liu, Ying Dong, Xiaolong Liu

Published in: Cancer Cell International | Issue 1/2019

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Abstract

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.
Appendix
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Metadata
Title
Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer
Authors
Jingbo Sun
Jingzhan Huang
Jin Lan
Kun Zhou
Yuan Gao
Zhigao Song
Yunyao Deng
Lixin Liu
Ying Dong
Xiaolong Liu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0986-8

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