Transcriptional Inactivation of TP53 and BMP Pathway Components Mediates Therapy-induced Dedifferentiation and Metastasis in Prostate Cancer (ChIP-seq)

AR blockade instigates two separate and complementary processes: 1) transcriptional silencing of TP53 and hence acquisition of hybrid E/M and stem-like traits; and 2) inhibition of the BMP signaling, which promotes resistance to the pro-apoptotic and anti-proliferative effects of AR inhibition. The drug tolerant prostate cancer cells generated through reprogramming are rescued by neuregulin and generate metastases in mice. Overall design: Bulk ChIP sequencing of the samples from various time points over the course of enzalutamide treatment of human prostate adenocarcinoma cells LNCaP.