ArticleEMBO molecular medicine2024
Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple-negative breast cancer.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Neurotransmitter receptor-associated gene signature: prognostic and immunosuppressive microenvironment in NSCLC.Future science OA · 2026Article
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Nanoparticle-Mediated TIPE1 mRNA Delivery Enhances Paclitaxel Sensitivity in Triple-Negative Breast Cancer by Modulating RAB7A Ubiquitination-Associated Stability and Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
- The role of pluripotency regulators in triple-negative breast cancer immune response.Frontiers in genetics · 2026Review
- Notch1 regulates Orai1 and Orai3 expression in breast cancer cells.Scientific reports · 2025Article
- A CD24BMC biology · 2025Article
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- Identification and Validation of Th1-Selective Epitopes Derived from Proteins Overexpressed in Breast Cancer Stem Cells.Vaccines · 2025Article
- The role of notch signaling pathway and non-coding RNAs in cancer and inflammation: progress, therapeutic insights, and future directions.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cell plasticity contributes significantly to the failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a genome-wide CRISPR-Cas9 screen, we investigated escape mechanisms of NOTCH-driven TNBC treated with a gamma-secretase inhibitor (GSI) and identified SOX2 as a target of resistance to Notch inhibition. We describe a novel reciprocal inhibitory feedback mechanism between Notch signaling and SOX2. Specifically, Notch signaling inhibits SOX2 expression through its target genes of the HEY family, and SOX2 inhibits Notch signaling through direct interaction with RBPJ. This mechanism shapes divergent cell states with NOTCH positive TNBC being more epithelial-like, while SOX2 expression correlates with epithelial-mesenchymal transition, induces cancer stem cell features and GSI resistance. To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second-line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.
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