Contribution of common plastic-related endocrine disruptors to epithelial-mesenchymal transition (EMT) and tumor progression

Abstract

Many chemicals, including many endocrine disruptors (EDCs) are known to leach out from various plastic consumer products and waste, and are widespread in the environment. EDCs are a large group of contaminants that can interfere with hormonal metabolism or function. In addition, there are in the literature implications of contribution by EDCs in tumor progression, the last stage of carcinogenesis driven by cells with a metastatic phenotype. The process of epithelial cells losing their apical-basal polarity and cell-to-cell contacts, and acquiring migration and invasive properties typical of mesenchymal cells is called epithelial-mesenchymal transition (EMT). It is essential for tumor progression. In human cells, plastic-related EDCs, (phthalates, bisphenol A, and the alkylphenols: nonylphenol and octylphenol) reduce epithelial E-cadherin, and increase mesenchymal N-cadherin and extracellular matrix metalloproteinases. These changes are hallmarks of EMT. In xenograft mouse studies, EDCs increase migration of cells and metastatic growth in distant tissues. Their contribution to EMT and tumor progression, the topic of this review, is important from public health perspective, because of the ubiquitous exposure to these EDCs. In this mini-review we also discuss molecular mechanisms associated with EDC-induced EMT and tumor progression.

Keywords: Alkylphenols; Bisphenol A; E-cadherin, N-cadherin; EMT; Hallmarks of EMT; Phthalates.