FOXA1 inhibits prostate cancer hypoxia program through transcriptional repression of HIF1A

We and others have previously shown FOXA1 is frequently mutated or downregulated in castration resistant prostate cancer (CRPC). Here we report a novel role for transcription factor FOXA1 in directly repressing HIF1A expression in prostate cancer cells. FOXA1 knockdown induced the expression of HIF1A and hypoxia signature genes, which were reduced by concomitant HIF1A knockdown or treatment with HIF1A inhibitor KC7F2. Thus, our data suggest FOXA1 loss induces aberrant hypoxia signaling and tumor progression in part via HIF1A. Overall design: Examination of transcriptional reprogramming in human prostate cancer LNCaP cells following FOXA1 knockdown with or without concomitant genetic/pharmacological inhibition of HIF1A. Cells were treated with 100µM CoCl2 to mimic tumor hypoxia and stabilize HIF1A protein when expressed. There are 18 RNA-seq samples with pGIPZ as control. Each condition was performed in triplicate.