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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE156789 | GEO | 2020/08/25

REPOSITORIES: GEO

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AP-1 dependent changes in chromatin accessibility in resistant basal cell carcinoma cell line

Project description: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 transcription factor activity is essential to maintain MRTF activation. Here, we treat a murine BCC cell line with small molecule AP-1 inhibitor and analyze chromatin accessibility profiles.

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Analysis of AP-1 regulation on Smad3 genome-wide DNA binding sites in resistant basal cell carcinoma

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Genome-wide chromatin accessibility analysis of MRTF-active subpopulations in human basal cell carcinoma

Project description: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. Here, we use three surface markers (LYPD3, TACSTD2, and LY6D) to isolate the nMRTF subpopulation and analyze chromatin accessibility profiles.

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