1,2-Naphthoquinone promotes cell migration through EGFR-ERK signaling pathway in human A549 cells

Abstract

Hazardous environmental factors contribute to various irreversible threats to human health worldwide. Accumulating evidence suggests that exposure to particulate matter with an aerodynamic diameter of <2.5 µm (PM_2.5) plays a critical role in lung carcinogenesis. Previously, we reported that 1,2-naphthoquinone (1,2-NQ), a component of atmospheric PM_2.5 and diesel exhaust particles, forms a covalent bond with the epidermal growth factor receptor (EGFR) via protein N-arylation, thereby activating the downstream protein kinase B (Akt) signaling pathway. Here, we elucidate a regulatory mechanism by which 1,2-NQ modulates the migratory activity of human lung adenocarcinoma A549 cells. Specifically, exposure of A549 cells to 1,2-NQ induces phosphorylation of EGFR, leading to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). This activation is significantly suppressed by anti-EGFR antibodies (cetuximab and panitumumab) and inhibitors targeting rapidly accelerated fibrosarcoma (Raf; LY3009120) and mitogen-activated protein kinase kinase (MEK; U0126). These findings suggest that 1,2-NQ induces ERK1/2 phosphorylation by activating the Raf-MEK pathway. Notably, suppression of EGFR-ERK1/2 signaling resulted in a decrease in migratory activity. Our findings provide new insights into lung cancer carcinogenesis and may contribute to the development of novel therapeutic strategies.