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Full Length Article | Open Access

SOX4 contributes to TGF-β-induced epithelial–mesenchymal transition and stem cell characteristics of gastric cancer cells

Xudong Penga, Guangyi Liua, Hongxia Pengb, Anqi Chena, Lang Zhaa, Ziwei Wanga,( )
Gastrointestinal Surgical Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
Department of General Surgery, The First People's Hospital, Yibin, Sichuan, 644000 China

Peer review under responsibility of Chongqing Medical University.

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An erratum to this article is available online at:
https://doi.org/10.1016/j.gendis.2021.03.001

Abstract

SOX4 is highly expressed in gastric cancer (GC) and is associated with tumor grade, metastasis and prognosis, however the mechanism is not clear. We report herein that SOX4 was upregulated and overexpression of SOX4 was associated with increased expression of the markers of Epithelial–mesenchymal transition (EMT) and stemness in clinic patient samples. In vitro, overexpression of SOX4 promoted the invasion as showed by Transwell assay and stemness of GC cells as assessed by sphere formation assay, which was suppressed by silencing SOX4 with shRNA. Further studies showed that SOX4 up-regulated the expression of EMT transcription factors Twist1, snail1 and zeb1 and stemness transcription factors SOX2 and OCT4, and promoted the nuclear translocation of β-catenin. Moreover, we revealed that TGF-β treatment significantly up-regulated the expression of SOX4 and silencing SOX4 reversed TGF-β induced invasion and sphere formation ability of GC cells. Finally, we showed that SOX4 promoted the lung metastasis and tumor formation ability of gastric cancer cells in nude mice. Our results suggest that SOX4 is a target TGF-β signaling and mediates TGF-β-induced EMT and stem cell characteristics of GC cells, revealing a novel role of TGF-β/SOX4 axis in the regulation of malignant behavior of GC.

Keywords

Gastric cancerStemnessEpithelial–mesenchymal transitionSOX4TGF-β

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Genes & Diseases
Volume 5 Issue 1,
March 2018
Pages 49-61
DOI: 10.1016/j.gendis.2017.12.005
Cite this article:
Peng X, Liu G, Peng H, et al. SOX4 contributes to TGF-β-induced epithelial–mesenchymal transition and stem cell characteristics of gastric cancer cells. Genes & Diseases, 2018, 5(1): 49-61. https://doi.org/10.1016/j.gendis.2017.12.005

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Received: 19 October 2017
Accepted: 11 December 2017
Published: 26 December 2017
© 2018, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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