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Title: Cadmium stimulates metastasis-associated phenotype in triple-negative breast cancer cells through integrin and β-catenin signaling

Abstract

Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1 μM Cd increased cell spreading and cell migration. This was associated with the activation of integrin β1, FAK, Src, and Rac1. Treatment with Cd also inhibited GSK3β activity and induced T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription, indicating the involvement of β-catenin signaling. Furthermore, treatment with 3 μM Cd for 4 weeks increased the expression of β-catenin and enhanced TCF/LEF-mediated transcription. Furthermore, enhanced expressions of integrins α5 and β1, paxillin, and vimentin indicated that prolonged Cd treatment reorganized the cytoskeleton, which aided malignancy, as evidenced by enhanced matrix metalloprotease 2/9 (MMP2/9) secretion and cell invasion. Prolonged Cd treatment also caused an increase in cell growth. Together, these results indicate that Cd alters key signaling processes involved in the regulation of cytoskeleton to enhance cancer cell migration, invasion, adhesion,more » and proliferation. - Highlights: • Cd enhances cell adhesion in triple-negative breast cancer cells through integrin activation. • Inhibition of GSK3β by Cd leads to activation of β-catenin pathway. • Accumulation of β-catenin facilitates TCF/LEF-mediated-transcription. • Prolonged Cd treatment stimulates cell migration, invasion, and proliferation.« less

Authors:
Publication Date:
OSTI Identifier:
22722885
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 328; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; CADMIUM; HEAVY METALS; MAMMARY GLANDS; METASTASES; MIGRATION; NEOPLASMS; PHENOTYPE; PLANT GROWTH; SIGNALS

Citation Formats

Wei, Zhengxi, and Shaikh, Zahir A., E-mail: zshaikh@uri.edu. Cadmium stimulates metastasis-associated phenotype in triple-negative breast cancer cells through integrin and β-catenin signaling. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.05.017.
Wei, Zhengxi, & Shaikh, Zahir A., E-mail: zshaikh@uri.edu. Cadmium stimulates metastasis-associated phenotype in triple-negative breast cancer cells through integrin and β-catenin signaling. United States. https://doi.org/10.1016/J.TAAP.2017.05.017
Wei, Zhengxi, and Shaikh, Zahir A., E-mail: zshaikh@uri.edu. Tue . "Cadmium stimulates metastasis-associated phenotype in triple-negative breast cancer cells through integrin and β-catenin signaling". United States. https://doi.org/10.1016/J.TAAP.2017.05.017.
@article{osti_22722885,
title = {Cadmium stimulates metastasis-associated phenotype in triple-negative breast cancer cells through integrin and β-catenin signaling},
author = {Wei, Zhengxi and Shaikh, Zahir A., E-mail: zshaikh@uri.edu},
abstractNote = {Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1 μM Cd increased cell spreading and cell migration. This was associated with the activation of integrin β1, FAK, Src, and Rac1. Treatment with Cd also inhibited GSK3β activity and induced T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription, indicating the involvement of β-catenin signaling. Furthermore, treatment with 3 μM Cd for 4 weeks increased the expression of β-catenin and enhanced TCF/LEF-mediated transcription. Furthermore, enhanced expressions of integrins α5 and β1, paxillin, and vimentin indicated that prolonged Cd treatment reorganized the cytoskeleton, which aided malignancy, as evidenced by enhanced matrix metalloprotease 2/9 (MMP2/9) secretion and cell invasion. Prolonged Cd treatment also caused an increase in cell growth. Together, these results indicate that Cd alters key signaling processes involved in the regulation of cytoskeleton to enhance cancer cell migration, invasion, adhesion, and proliferation. - Highlights: • Cd enhances cell adhesion in triple-negative breast cancer cells through integrin activation. • Inhibition of GSK3β by Cd leads to activation of β-catenin pathway. • Accumulation of β-catenin facilitates TCF/LEF-mediated-transcription. • Prolonged Cd treatment stimulates cell migration, invasion, and proliferation.},
doi = {10.1016/J.TAAP.2017.05.017},
url = {https://www.osti.gov/biblio/22722885}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 328,
place = {United States},
year = {2017},
month = {8}
}