Cigarette smoke‐stimulated epithelial‐mesenchymal transition through Src activation

Abstract

Epithelial‐mesenchymal transition (EMT) is implicated in the pathogenesis of lung fibrosis and cancer metastasis, both associated with cigarette smoke (CS). CS, the major cause of lung cancer CS has been reported to promote EMT. Nonetheless, the mechanism whereby CS induces EMT remains largely unknown. We investigated the induction of EMT by CS and explored the underlying mechanisms in the human non‐small cell lung carcinoma (H358) cell line. We demonstrate that CS exposure decreases E‐cadherin and increases N‐cadherin and vimentin, markers of EMT. Pretreatment with N‐acetyl cysteine (NAC), a potent antioxidant and precursor of glutathione, abrogated changes in these EMT markers. Furthermore, CS activated Src kinase (shown as increased phosphorylation of Src at Tyr418) and the Src kinase inhibitor, PP2, inhibited CS‐stimulated EMT changes, suggesting that Src is critical in CS‐stimulated EMT induction. NAC addition to the medium abrogated CS‐stimulated Src activation. Catalase had no effect on Src activation at 5 min of CS exposure, but abrogated it at 5 min. Taken together, these data suggest that CS initiates EMT through Src, which is activated by CS through oxidation or alkylation.