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Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Gastric Cancer | Primary research

Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness

Authors: Chuanqian Huang, Renli Chen, Fangjing Zheng, Yirong Tang, Xiukang Wang, Zichun Chen, Xiaolan Lai

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression.

Methods

To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial–mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model.

Results

We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model.

Conclusion

Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.
Appendix
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Metadata
Title
Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness
Authors
Chuanqian Huang
Renli Chen
Fangjing Zheng
Yirong Tang
Xiukang Wang
Zichun Chen
Xiaolan Lai
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-01828-9

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