ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting the NOTCH2/ADAM10/TCF7L2 Axis-Mediated Transcriptional Regulation of Wnt Pathway Suppresses Tumor Growth and Enhances Chemosensitivity in Colorectal Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Expression ofInternational journal of molecular sciences · 2026Article
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- STRAP promotes hepatocellular carcinoma progression through activation of an STRAP/Wnt-β-catenin/STRAP positive feedback loop.iScience · 2026Article
- Multimodal activity-affinity assay of ADAM-10 extracellular vesicles in untreated plasma reveals metastatic stage of colorectal cancer.Biosensors & bioelectronics · 2026Article
- Myeloid-Specific Deletion ofBiomedicines · 2026Article
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- SCMO: a deep learning model integrating the single-cell resolution TME ecosystem and multi-omics for survival prediction in CRC patients.Journal of translational medicine · 2026Article
- PDK4-driven metabolic reprogramming enhances mesothelial cell invasion in colorectal cancer peritoneal metastasis.Acta biochimica et biophysica Sinica · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Bridging metabolic reprogramming and targeted therapy: the critical role of S-palmitoylation in cancer.Frontiers in cell and developmental biology · 2026Review
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Mechanistic insights into the lncRNA-Notch signaling axis in tumors.Frontiers in cell and developmental biology · 2026Review
- Targeting menin in lysine methyltransferase 2A/nucleophosmin-mutated leukemia: A novel strategy from epigenetic dysregulation to clinical therapy (Review).Oncology letters · 2025Review
- Recent advances and challenges in colorectal cancer: From molecular research to treatment.World journal of gastroenterology · 2025Review
- Targeting the NOTCH2/ADAM10/TCF7L2 Axis-Mediated Transcriptional Regulation of Wnt Pathway Suppresses Tumor Growth and Enhances Chemosensitivity in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- tRNA-derived small RNA 3' tRF-Ala CGC obstructs NK cytotoxicity via cleavage of membrane protein MICA in colorectal cancer.Frontiers in immunology · 2025Article
- LOX1-mediated supramolecular self-assembly nanomedicine for microsatellite-stable colorectal cancer towards reactivating anti-tumor immunity.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Wnt/β-catenin/transcription factor (TCF) transcriptional activity plays an integral role in colorectal cancer (CRC) carcinogenesis. However, to date, no drugs targeting this pathway are used in clinical practice owing to the undesirable and serious side effects. In this study, it is found that the transcriptional regulation of Wnt pathway is activated and associated with liver metastasis in CRC. Through high-throughput screening of 24 inhibitors on 12 CRC and three colorectal organoids in this organoid living biobank, adavivint is found to exhibit anti-tumor activity and low toxicity in colorectal organoids, independent of the canonical Wnt/β-catenin signaling. Mechanistically, ADAM10 is screened as a target of adavivint to specifically regulate the protein expression of NOTCH2, which mediates the transcriptional regulation of the Wnt pathway. NOTCH2 not directly interact with TCF7-like 2 (TCF7L2), a key downstream transcriptional factor of canonical Wnt/β-catenin signaling, but directly activated the transcription of TCF7L2 and Wnt target genes, such as MYC, JUN and CCND1/2. Furthermore, use of adavivint or blockage of ADAM10/NOTCH2/TCF7L2 signaling enhances the chemosensitivity of CRC cells. Overall, this study provides a promising candidate for the development of small-molecule inhibitors and reveals a potential therapeutic target for CRC.
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Registered trials
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