Aryl hydrocarbon receptor suppresses lung cancer metastasis

Lung cancer mortality largely results from metastasis. Despite curative surgery many patients with early stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background we functionally screened for novel metastasis modulators using a barcoded shRNA library and an orthotopic lung cancer model. We identified aryl hydrocarbon receptor (AHR), a sensor of xenobiotic chemicals and transcription factor, as suppressor of lung cancer metastasis.In order to identify those AHR effectors involved in the modulation of metastatic processes, we devised mRNA sequencing in H1975 cells with and without shRNA-mediated suppression of endogenous AHR (H1975 shAHR-K2 and H1975 shScr, respectively). To further discriminate between intrinsic and ligand-induced AHR regulation, we studied the impact of the AHR activator omeprazole on RNA expression profiles.