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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

The epigenetically downregulated factor CYGB suppresses breast cancer through inhibition of glucose metabolism

Authors: Yixiao Feng, Mingjun Wu, Shuman Li, Xiaoqian He, Jun Tang, Weiyan Peng, Beilei Zeng, Chuxia Deng, Guosheng Ren, Tingxiu Xiang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Recent studies suggested the globin family member cytoglobin (CYGB) as a potential tumor suppressor; however, the mechanism by which CYGB suppresses cancer is elusive. We investigated the role and mechanism of CYGB in suppressing breast cancer.

Methods

CYGB expression was examined by reverse transcription PCR, quantitative reverse transcription PCR and open database analysis. Promoter methylation was examined by methylation-specific PCR. Metabolomics and proteomics were analyzed by gas chromatography-mass spectrometry and isobaric tags for relative and absolute quantitation, respectively. The effects and mechanisms of ectopic CYGB expression in breast cancer cells were assessed with molecular biological and cellular approaches in vitro and with a xenograft tumor model in nude mice.

Results

CYGB expression was downregulated in breast cancer tissues and cell lines, which was associated with promoter methylation. Ectopic CYGB expression suppressed proliferation, migration, invasion and induced apoptosis in breast cancer cell lines MCF7 (p53WT) and MB231 (p53mt) in vitro, and inhibited xenograft tumor growth in vivo. By proteomics and metabolomics analysis, glucose metabolism was found to be one of the main pathways suppressed by CYGB. The CYGB-expressing cells had lower ATP and compromised glycolysis. Additionally, CYGB suppressed key glucose metabolism factors including GLUT1 and HXK2 in p53-dependent and -independent manners. Restoration of GLUT1 or HXK2 expression attenuated CYGB-mediated proliferation suppression and apoptosis induction.

Conclusions

CYGB is a potential tumor suppressor in breast cancer that is epigenetically suppressed. The results for the first time suggest that CYGB suppresses breast cancer through inhibiting glucose metabolism, which could be exploited for breast cancer prevention and therapy.
Appendix
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Metadata
Title
The epigenetically downregulated factor CYGB suppresses breast cancer through inhibition of glucose metabolism
Authors
Yixiao Feng
Mingjun Wu
Shuman Li
Xiaoqian He
Jun Tang
Weiyan Peng
Beilei Zeng
Chuxia Deng
Guosheng Ren
Tingxiu Xiang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0979-9

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