AP-1 and TGFb-dependent transcriptomic changes in resistant basal cell carcinoma cell line

Tumor heterogeneity and lack of knowledge about resistant cell states remain a significant barrier to effective targeted cancer therapies. Basal cell carcinomas (BCCs) uniformly depend on Hedgehog (Hh)/Gli signaling for cell growth. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies Gli1 activity, but nMRTF cell state and key factors driving its accumulation remain unknown. We have determined that AP-1 and TGFb transcription factor activity is essential to maintain MRTF activation. Here, we treat a murine BCC cell line with small molecule AP-1 and ALK5 inhibitors and analyze transcriptomic profiles. ASZ001 cells were plated and serum-starved and treated with 20 uM of AP-1 inhibitor T-5224 or 10 uM of ALK5 inhibitor SB431542 for 24 hours, then processed for ATAC-seq. Two or three biological replicates were sequenced per treatment group.