ArticleNature communications2020
AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Fra-2 controls the response to the KRAS inhibitor MRTX-1133 in pancreatic ductal adenocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Does Basal Cell Carcinoma Arise from a Precursor Lesion?The Journal of investigative dermatology · 2026Review
- Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors.The journal of pathology. Clinical research · 2026Article
- Review
- Epigenomic regulation of stemness contributes to the low immunogenicity of the most mutated human cancer.Cell reports · 2025Article
- Application of transcriptomics techniques in skin cancer.Frontiers in oncology · 2025Review
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Application of large-scale and multicohort plasma proteomics data to discover novel causal proteins in gastric cancer.Discover oncology · 2024Article
- Basal-to-inflammatory transition and tumor resistance via crosstalk with a pro-inflammatory stromal niche.Nature communications · 2024Article
- Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Acquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition.The Journal of investigative dermatology · 2024Article
- Stem-cell states converge in multistage cutaneous squamous cell carcinoma development.Science (New York, N.Y.) · 2024Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Role of Fra-2 in cancer.Cell death and differentiation · 2024Review
- Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology.Frontiers in oncology · 2024Review
- Comprehensive analysis of resistance mechanisms to EGFR-TKIs and establishment and validation of prognostic model.Journal of cancer research and clinical oncology · 2023Article
- Review
- The role of TGF-β and antimicrobial peptides in basal cell carcinoma: a systematic review.Postepy dermatologii i alergologii · 2023Review
- Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.