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Review
. 2022 Jul 27;22(1):237.
doi: 10.1186/s12935-022-02638-3.

Toxic metals in the regulation of epithelial-mesenchymal plasticity: demons or angels?

Xu-Li Chen #  1 , Yan-Ming Xu #  1 , Andy T Y Lau  2
Affiliations
Review

Toxic metals in the regulation of epithelial-mesenchymal plasticity: demons or angels?

Xu-Li Chen et al. Cancer Cell Int. .

Abstract

Epithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial-mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.

Keywords: Arsenic; Cadmium; Chromium; Cobalt; Copper; EMT; Nickel; Toxicologically relevant metals.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
An overview of the EMT process and classic gene markers. The EMT is a dynamic and reversible process modulated by epithelial and mesenchymal marker expression: Some of the typical epithelial markers include β-catenin (CTNNB1) and E-cadherin (CDH1), whereas mesenchymal markers include N-cadherin (CDH2), SNAI1/2 (SNAI1/2), and vimentin (VIM). Studies have shown that toxicologically relevant metals such as AS, Cd, Co, Cr, Ni, and Cu can promote the progress of EMT, and three of these metals (AS, Cd, and Cu) may inhibit EMT
Fig. 2
Fig. 2
Health risks associated with the six heavy metals reviewed in this article. Chronic exposure to these metals could promote EMT and the development of cancers in the lung, breast, liver, kidney, bladder, and prostate
See this image and copyright information in PMC

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