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

Open Access 01-12-2019 | Gastric Cancer | Primary research

BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway

Authors: Xiao-Feng Xu, Feng Gao, Jian-Jiang Wang, Cong Long, Xing Chen, Lan Tao, Liu Yang, Li Ding, Yong Ji

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Cancer stem cells (CSCs), drug-resistant cancer cell subsets, are known to be responsible for tumor metastasis and relapse. The JAK/STAT pathway, activated by SH2 domain, is known to regulate the tumor growth in gastric cancer (GC). Now, this study was designed to examine whether BMX-ARHGAP affects the GC stem cell properties and the underlying regulatory network via JAK/STAT axis.

Methods

BMX-ARHGAP expression was characterized in GC tissues and cells by RT-qPCR and western blot assay. When BMX-ARHGAP was overexpressed or silenced via plasmids or siRNA transfection, the stem cell properties were assessed by determining stem cell markers CD133, CD44, SOX2 and Nanog, followed by cell sphere and colony formation assays. Subsequently, cell proliferation and invasion were examined by conducting EdU and Transwell assays. The JAK/STAT3 signaling pathway activation was inhibited using AG490. ARHGAP12, BMX exon 10–11, BXM-SH2, JAK2 and STAT3 expression patterns were all determined to examine the regulatory network. The stem cell property in nude mice was also tested.

Results

BMX-ARHGAP was determined to be enriched in the GC. Overexpression of BMX-ARHGAP resulted in increased expression of CD133, CD44, SOX2 and Nanog protein, and accelerated proliferation and invasion of CD133+CD44+ cells as well as facilitated self-renewal potential of GC cells. However, the inhibition of the JAK/STAT3 signaling pathway reversed the stimulating effect of BMX-ARHGAP on proliferative and invasion abilities of CD133+CD44+ cells. The overexpression of BMX-ARHGAP was suggested to increase the BMX-SH2 protein expression via ARHGAP 5′UTR, and activate the JAK/STAT3 signaling pathway. Also, BMX-ARHGAP promoted tumor growth in nude mice.

Conclusions

The aforementioned results demonstrated that the BMX-ARHGAP-dependent SH2 domain-JAK/STAT3 axis mediates the maintenance of GC stem cells, benefiting the development of new potential therapeutic targets for GC.
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Metadata
Title
BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway
Authors
Xiao-Feng Xu
Feng Gao
Jian-Jiang Wang
Cong Long
Xing Chen
Lan Tao
Liu Yang
Li Ding
Yong Ji
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/s12935-019-0847-5

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