ArticleCancer research2025
LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Single-cell epigenomics of colorectal cancer.Experimental & molecular medicine · 2026Review
- Gastrointestinal conventional carcinoma with neuroendocrine differentiation: From pathological phenomenon to clinical importance (Review).Oncology letters · 2026Review
- DNA Methyltransferase Inhibition Prevents Platinum-Induced Ovarian Cancer Stem Cell Enrichment.Cancer research communications · 2026Article
- Inhibition of histone demethylase LSD1 suppresses CD47 expression and enhances efficacy of CD47 blockade in breast cancer.Journal for immunotherapy of cancer · 2026Article
- Dual Targeting of EZH2 and LSD1 Suppresses Hepatocellular Carcinoma via Disruption of Sonic Hedgehog Signaling.International journal of molecular sciences · 2026Article
- The applications of single-cell multiomics in drug screening.Pharmaceutical science advances · 2025Review
- Mast cells interact directly with colorectal cancer cells to promote epithelial-to-mesenchymal transition.Oncogene · 2025Article
- Review
- Targeting mitochondrial ribosomal protein expression by andrographolide and melatonin for colon cancer treatment.Cancer letters · 2025Article
- LSD1 inhibition attenuates targeted therapy-induced lineage plasticity in BRAF mutant colorectal cancer.Molecular cancer · 2025Article
- Demystifying the Role of Histone Demethylases in Colorectal Cancer: Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2025Review
- circ0066187 promotes pulmonary fibrogenesis through targeting STAT3-mediated metabolism signal pathway.Cellular and molecular life sciences : CMLS · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Neuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EEC), the neuroendocrine cells of the normal colon epithelium, as compared with non-mCRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. In this study, single-cell multiomics uncovered epigenetic alterations that accompany EEC differentiation, identified STAT3 as a regulator of EEC specification, and discovered a rare cancer-specific cell type with enteric neuron-like characteristics. Furthermore, lysine-specific demethylase 1 (LSD1) and CoREST2 mediated STAT3 demethylation and enhanced STAT3 chromatin binding. Knockdown of CoREST2 in an orthotopic xenograft mouse model resulted in decreased primary tumor growth and lung metastases. Collectively, these results provide a rationale for developing LSD1 inhibitors that target the interaction between LSD1 and STAT3 or CoREST2, which may improve clinical outcomes for patients with mCRC. Significance: STAT3 activity mediated by LSD1 and CoREST2 induces enteroendocrine cell specification in mucinous colorectal cancer, suggesting disrupting interaction among LSD1, CoREST2, and STAT3 as a therapeutic strategy to target neuroendocrine differentiation.
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