Pentachlorophenol enhances bladder cancer cell invasion through altered protein stability.

Pentachlorophenol (PCP) is a persistent environmental contaminant, but its effect on bladder cancer invasiveness is unclear. Here, we show that environmentally relevant PCP concentrations enhance invasion of T24 and SW780 bladder cancer cells, with limited effects on migration or proliferation. Integrative target prediction, transcriptomics, and machine learning identified EGFR, MAP2K1, and NFE2L2 as candidate contributors. PCP altered the protein stability of these factors, and EGFR or MAP2K1 knockdown or NFE2L2 overexpression partially attenuated PCP-induced invasion. A three-gene signature based on these factors was associated with poor prognosis across five bladder cancer cohorts, although these datasets lacked PCP exposure information. Molecular docking and molecular dynamics simulations predicted compatible interactions between PCP and the three proteins. Together, these findings identify candidate molecular contributors to PCP-associated bladder cancer invasion and support further chronic-exposure and in vivo studies.