ArticleCancer research2023
β-Catenin-Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Frequent antecedent nodules and diagnostic gaps in adrenocortical carcinoma.Journal of the Endocrine Society · 2026Article
- Distinct Transcriptional Programs Controlled byMedical sciences (Basel, Switzerland) · 2026Article
- Molecular subtyping of adrenocortical carcinoma reveals distinct subtypes with prognostic and therapeutic implications.Endocrine-related cancer · 2026Article
- Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion.Scientific reports · 2026Article
- Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis.bioRxiv : the preprint server for biology · 2025Article
- β-catenin functions as a molecular adapter for disordered cBAF interactions.Molecular cell · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- Bimodal Genomic Approach Predicting Semaphorin 7A (SEMA7A) as Prognostic Biomarker in Adrenocortical Carcinoma.Cancers · 2025Article
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.Cancer communications (London, England) · 2025Article
- Bimodal genomic approach predicting Semaphorin 7A (SEMA7A) as prognostic biomarker in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2025Article
- The Wild West of spike-in normalization.Nature biotechnology · 2024Article
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Age-related Changes in the Adrenal Cortex: Insights and Implications.Journal of the Endocrine Society · 2023Review
- Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth.Cancers · 2023Article
- A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma.Frontiers in endocrinology · 2023Article
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Authors and funding
30 authors.
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Abstract
Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin-activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific β-catenin-containing complexes, and the epigenome. On chromatin, β-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, β-catenin bound histone methyltransferase EZH2. SF1/β-catenin and EZH2/β-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/β-catenin from chromatin and favored EZH2/β-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities. SIGNIFICANCE: Oncogenic β-catenin can use tissue-specific partners to regulate cellular differentiation programs that can be reversed by epigenetic therapies, identifying epigenetic control of differentiation as a viable target for β-catenin-driven cancers.
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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.