Chronic Exposure to Benzo[a]pyrene and Catechol Drives Lung Cancer Invasion via Convergent Extracellular Matrix Remodeling and Metabolic Reprogramming

ABSTRACT

Chronic low‐level exposure to environmentally relevant pollutants is a widespread yet underappreciated risk factor in cancer progression. This study aimed to determine whether prolonged exposure to benzo[a]pyrene (B[a]P) and catechol (CL) enhanced malignant phenotypes in human lung cancer A549 cells. Following 3 months of exposure plus an additional month of maintenance culture, cells treated with either pollutant exhibited persistently increased migration, invasion, and colony formation. Integrated transcriptomic and proteomic profiling revealed consistent upregulation of extracellular matrix remodeling and glycolytic pathways. Among the commonly elevated targets, four showing the most significant upregulation ( LOX , CLDN1 , HK2 , and SLC2A1 , with the latter encoding GLUT1) were identified and verified by qRT‐PCR and western blotting. Knockdown of each candidate markedly reduced the pollutant‐induced migratory and invasive capacities, with GLUT1 silencing showing the strongest effect. Moreover, high expression of these four genes correlated with worse survival outcomes in lung cancer patients. Collectively, these results indicated that chronic exposure to structurally distinct pollutants promoted lung cancer invasion through convergent upregulation of LOX, CLDN1, HK2, and GLUT1, highlighting them as potential prognostic biomarkers and therapeutic targets.