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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Research article

Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation

Authors: Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chang Dong Yeo, Chan Kwon Park, Young Kyoon Kim, Tae-Jung Kim, Seong-Beom Lee, Sug Hyung Lee, Jong Y. Park, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood.

Methods

Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed. For validation, the EMT and stem cell characteristics were analyzed. To determine whether an epigenetic mechanism was involved, the cell lines were treated with a DNA methyltransferase inhibitor (AZA), and methylation-specific PCR and bisulfite sequencing were performed.

Results

Next-generation sequencing revealed that the CXCR4 expression was significantly higher after the hypoxic condition, which functionally resulted in the EMT and cancer stemness acquisition. The acquisition of the EMT and stemness properties was inhibited by treatment with CXCR4 siRNA. The CXCR4 was activated by either the hypoxic condition or treatment with AZA. The methylation-specific PCR and bisulfite sequencing displayed a decreased CXCR4 promoter methylation in the hypoxic condition.

Conclusions

These results suggest that hypoxia-induced acquisition of cancer stem cell characteristics was associated with CXCR4 activation by its aberrant promoter demethylation.
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Metadata
Title
Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation
Authors
Nahyeon Kang
Su Yeon Choi
Bit Na Kim
Chang Dong Yeo
Chan Kwon Park
Young Kyoon Kim
Tae-Jung Kim
Seong-Beom Lee
Sug Hyung Lee
Jong Y. Park
Mi Sun Park
Hyeon Woo Yim
Seung Joon Kim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5360-7

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