Sulfate Aerosols Promote Lung Cancer Metastasis by Epigenetically Regulating the Epithelial-to-Mesenchymal Transition (EMT),Environmental Science & Technology

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Sulfate Aerosols Promote Lung Cancer Metastasis by Epigenetically Regulating the Epithelial-to-Mesenchymal Transition (EMT)
Environmental Science & Technology ( IF 11.4 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1021/acs.est.7b02857
Yang Yun ₁ , Rui Gao ₁ , Huifeng Yue ₁ , Lin Guo ₁ , Guangke Li ₁ , Nan Sang ₁

Affiliation

Secondary inorganic aerosols (SIA), particularly sulfate aerosols, are central particulate matter (PM) constituents of severe haze formation in China and exert profound impacts on human health; however, our understanding of the mechanisms by which sulfate aerosols cause malignancy in lung carcinogenesis remains incomplete. Here, we show that exposure to secondary inorganic aerosols induced the invasion and migration of lung epithelial cells, and that (NH₄)₂SO₄ exerted the most serious effects in vitro and promoted lung tumor metastasis in vivo. This action was associated with alterations of phenotype markers in the epithelial-to-mesenchymal transition (EMT), such as the up-regulation of fibronectin (Fn1) and the down-regulation of E-cadherin (E-cad). Hypoxia-inducible factor 1α (HIF-1α)-Snail signaling, regulated by the generation of reactive oxygen species (ROS), was involved in the (NH₄)₂SO₄-induced EMT, and the potent antioxidant N-acetylcysteine (NAC) inhibited the activation of HIF-1α-Snail and blocked the EMT, cell invasion, and migration in response to (NH₄)₂SO₄. Additionally, CpG hypermethylation in the E-cad promoter regions partly contributed to the (NH₄)₂SO₄-regulated E-cad repression, and the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-Aza) restored the (NH₄)₂SO₄-induced down-regulation of E-cad. Our findings reveal a potential mechanistic basis for exploring the association between sulfate aerosol exposure and increased malignancy during lung carcinogenesis, and suggest new approaches for the treatment, improvement, and prevention of lung cancer resulting from sulfate aerosol exposure in severe haze-fog.

更新日期：2017-09-13

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