Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway

DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in s...

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Main Authors: XianYi Zhou, JiuLin Li, XiuYong Liao, ChengYu Ding, SaiJiao Na, JiangRong Du, QingHui Meng, Peng Zheng, Fan Sun
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Advances in Cancer Biology - Metastasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667394025000127
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author XianYi Zhou
JiuLin Li
XiuYong Liao
ChengYu Ding
SaiJiao Na
JiangRong Du
QingHui Meng
Peng Zheng
Fan Sun
author_facet XianYi Zhou
JiuLin Li
XiuYong Liao
ChengYu Ding
SaiJiao Na
JiangRong Du
QingHui Meng
Peng Zheng
Fan Sun
author_sort XianYi Zhou
collection DOAJ
description DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.
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id doaj-art-1cc3ff4e9bc546d7a64fc23c1550371d
institution Kabale University
issn 2667-3940
language English
publishDate 2025-12-01
publisher Elsevier
record_format Article
series Advances in Cancer Biology - Metastasis
spelling doaj-art-1cc3ff4e9bc546d7a64fc23c1550371d2025-08-20T03:29:10ZengElsevierAdvances in Cancer Biology - Metastasis2667-39402025-12-011510014310.1016/j.adcanc.2025.100143Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathwayXianYi Zhou0JiuLin Li1XiuYong Liao2ChengYu Ding3SaiJiao Na4JiangRong Du5QingHui Meng6Peng Zheng7Fan Sun8College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, ChinaCollege of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, ChinaQianjiang Central Hospital of Chongqing, Chongqing University Qianjiang Hospital, Chongqing, ChinaCollege of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, ChinaCollege of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, ChinaQianjiang Central Hospital of Chongqing, Chongqing University Qianjiang Hospital, Chongqing, ChinaQianjiang Central for Disease Control and Prevention, Chongqing, ChinaCollege of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China; Corresponding author.No. 2, Huangjia lake Road, Wuhan, 430065, China.College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China; Corresponding author.No. 2, Huangjia lake Road, Wuhan, 430065, China.DSF is a well-known alcohol withdrawal agent that has shown considerable anticancer effects in preclinical studies. In the present study, we aimed to elucidate the mechanism by which DSF and CTSB modulate of the migration and invasion of GCs. Our results illustrate that DSF plays a pivotal role in suppressing tumor migration, invasion, and EMT in GC by modulating CTSB expression. Furthermore, DSF was found to aggravate the reduction in β-catenin expression via GSK-3β, consequently inhibiting CTSB expression, which has a pronounced effect on invading gastric cancer cells as a metastasis-promoting gene. Notably, β-catenin was found to increase CTSB transcriptional activity by binding to the promoter of CTSB, leading to an increase in CTSB protein levels. Collectively, our findings elucidate the molecular mechanism by which DSF suppresses EMT, migration, and invasion in GC through the GSK-3β/β-catenin/CTSB pathway, underscoring the potential of CTSB as a therapeutic target for GC.http://www.sciencedirect.com/science/article/pii/S2667394025000127DSFCTSBβ-cateninMigrationInvasion
spellingShingle XianYi Zhou
JiuLin Li
XiuYong Liao
ChengYu Ding
SaiJiao Na
JiangRong Du
QingHui Meng
Peng Zheng
Fan Sun
Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
Advances in Cancer Biology - Metastasis
DSF
CTSB
β-catenin
Migration
Invasion
title Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
title_full Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
title_fullStr Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
title_full_unstemmed Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
title_short Disulfiram inhibits migration, invasion and epithelial-mesenchymal transition of gastric cancer cells via β-catenin/CTSB pathway
title_sort disulfiram inhibits migration invasion and epithelial mesenchymal transition of gastric cancer cells via β catenin ctsb pathway
topic DSF
CTSB
β-catenin
Migration
Invasion
url http://www.sciencedirect.com/science/article/pii/S2667394025000127
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