Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition
Inorganic arsenic is a Class I human Carcinogen. However, the role of chronic inorganic arsenic exposure on prostate cancer metastasis still unclear. This study aimed to investigate the effects and mechanism of chronic NaAsO2 exposure on migration and invasion of prostate cancer cells. DU145 and PC-...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000776 |
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| author | Zhi-Hui Zhang Hai-Xin Yan Ming-Dong Liu Feng-Wen Niu Kai Yao Shi-Yao Feng Xi Li Yuan-Hua Chen Dong-Dong Xie |
| author_facet | Zhi-Hui Zhang Hai-Xin Yan Ming-Dong Liu Feng-Wen Niu Kai Yao Shi-Yao Feng Xi Li Yuan-Hua Chen Dong-Dong Xie |
| author_sort | Zhi-Hui Zhang |
| collection | DOAJ |
| description | Inorganic arsenic is a Class I human Carcinogen. However, the role of chronic inorganic arsenic exposure on prostate cancer metastasis still unclear. This study aimed to investigate the effects and mechanism of chronic NaAsO2 exposure on migration and invasion of prostate cancer cells. DU145 and PC-3 cells were exposed to NaAsO2 (2 μM) for 25 generations. Wound healing and Transwell assays showed that chronic NaAsO2 exposure promoted migration and invasion of DU145 and PC-3 cells. In addition, chronic NaAsO2 exposure induced epithelial-mesenchymal transition (EMT) of DU145 cells by promoting β-catenin/TCF4 transcriptional activity. Mechanically, NaAsO2 promoted GSK-3β inactivation in the ''disruption complex'' through Akt- mediated phosphorylation at serine 9, and then inhibited the phosphorylation and ubiquitination degradation of β-catenin, which led to its nuclear translocation. Ly294002, a selective phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, suppressed the β-catenin/TCF4 complex activation and EMT through blocking Akt-mediated GSK-3β inactivation in the ''disruption complex'' in chronic NaAsO2 exposed DU145 and PC-3 cells. Moreover, Ly294002 alleviated chronic NaAsO2-induced migration and invasion in DU145 and PC-3 cells. These findings provide evidence that chronic arsenic exposure promotes migration and invasion of prostate cancer cells via an EMT mechanism driven by the AKT/GSK-3β/β-catenin/TCF4 signaling axis. Akt is expected to be a potential therapeutic target for chronic arsenic exposure-mediated prostate cancer metastasis. |
| format | Article |
| id | doaj-art-f501c5d054f546b5b5256c7307d01367 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-f501c5d054f546b5b5256c7307d013672025-02-12T05:30:09ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117741Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transitionZhi-Hui Zhang0Hai-Xin Yan1Ming-Dong Liu2Feng-Wen Niu3Kai Yao4Shi-Yao Feng5Xi Li6Yuan-Hua Chen7Dong-Dong Xie8Department of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; Corresponding author.Department of Urology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaDepartment of Urology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaDepartment of Histology and Embryology, Anhui Medical University, Hefei 230032, ChinaDepartment of Urology, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; Department of Urology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China; Corresponding author at: Department of Urology, Chaohu Hospital of Anhui Medical University, Chaohu 238000, China.Inorganic arsenic is a Class I human Carcinogen. However, the role of chronic inorganic arsenic exposure on prostate cancer metastasis still unclear. This study aimed to investigate the effects and mechanism of chronic NaAsO2 exposure on migration and invasion of prostate cancer cells. DU145 and PC-3 cells were exposed to NaAsO2 (2 μM) for 25 generations. Wound healing and Transwell assays showed that chronic NaAsO2 exposure promoted migration and invasion of DU145 and PC-3 cells. In addition, chronic NaAsO2 exposure induced epithelial-mesenchymal transition (EMT) of DU145 cells by promoting β-catenin/TCF4 transcriptional activity. Mechanically, NaAsO2 promoted GSK-3β inactivation in the ''disruption complex'' through Akt- mediated phosphorylation at serine 9, and then inhibited the phosphorylation and ubiquitination degradation of β-catenin, which led to its nuclear translocation. Ly294002, a selective phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, suppressed the β-catenin/TCF4 complex activation and EMT through blocking Akt-mediated GSK-3β inactivation in the ''disruption complex'' in chronic NaAsO2 exposed DU145 and PC-3 cells. Moreover, Ly294002 alleviated chronic NaAsO2-induced migration and invasion in DU145 and PC-3 cells. These findings provide evidence that chronic arsenic exposure promotes migration and invasion of prostate cancer cells via an EMT mechanism driven by the AKT/GSK-3β/β-catenin/TCF4 signaling axis. Akt is expected to be a potential therapeutic target for chronic arsenic exposure-mediated prostate cancer metastasis.http://www.sciencedirect.com/science/article/pii/S0147651325000776Prostate cancerChronic NaAsO2 exposureInvasionβ-catenin/TCF4Epithelial-mesenchymal transition |
| spellingShingle | Zhi-Hui Zhang Hai-Xin Yan Ming-Dong Liu Feng-Wen Niu Kai Yao Shi-Yao Feng Xi Li Yuan-Hua Chen Dong-Dong Xie Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition Ecotoxicology and Environmental Safety Prostate cancer Chronic NaAsO2 exposure Invasion β-catenin/TCF4 Epithelial-mesenchymal transition |
| title | Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition |
| title_full | Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition |
| title_fullStr | Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition |
| title_full_unstemmed | Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition |
| title_short | Chronic NaAsO2 exposure promotes migration and invasion of prostate cancer cells by Akt/GSK-3β/β-catenin/TCF4 axis-mediated epithelial-mesenchymal transition |
| title_sort | chronic naaso2 exposure promotes migration and invasion of prostate cancer cells by akt gsk 3β β catenin tcf4 axis mediated epithelial mesenchymal transition |
| topic | Prostate cancer Chronic NaAsO2 exposure Invasion β-catenin/TCF4 Epithelial-mesenchymal transition |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000776 |
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