ArticleProceedings of the National Academy of Sciences of the United States of America2011
Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 120 citations in OpenAlex.
- Auranofin Potentiates Cisplatin Response in the Setting of Context-Dependent NOTCH-Associated Signaling States in Endometrial Cancer.Cancer research communications · 2026Article
- A Robust Marine Collagen Peptide-Agarose 3D Culture System for In Vitro Modeling of Hepatocellular Carcinoma and Anti-Cancer Therapeutic Development.Marine drugs · 2025Article
- Notch1 and Major Vault Proteins Modulate Temozolomide Resistance in Glioblastoma.Journal of cellular and molecular medicine · 2025Article
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Evaluation of Notch1 and CD10 Expressions in Colorectal Carcinoma and Their Relationship with Prognosis.Iranian journal of pathology · 2025Article
- A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery.Marine drugs · 2024Article
- Correlation between trophoblast cell-surface antigen-2 (Trop-2) expression and pathological complete response in patients with HER2-positive early breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab.Breast cancer research and treatment · 2024Article
- Therapy-induced senescence in breast cancer: an overview.Exploration of targeted anti-tumor therapy · 2024Review
- Review
- Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.Frontiers in aging neuroscience · 2024Review
- The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance.International journal of molecular sciences · 2023Review
- LncRNA MALAT1 signaling pathway and clinical applications in overcome on cancers metastasis.Clinical and experimental medicine · 2023Review
- Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Possible New Histological Prognostic Index for Large B-Cell Lymphoma.Journal of clinical medicine · 2023Article
- Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective.Experimental & molecular medicine · 2023Review
- Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells.Cell death discovery · 2023Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.BMC cancer · 2023Article
- Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.International journal of molecular sciences · 2023Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.Research square · 2023Article
- Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells.Pharmaceutics · 2022Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Multidrug resistance (MDR) is a barrier to successful cancer chemotherapy. Although MDR is associated with overexpression of ATP-binding cassette (ABC) membrane transporters, mechanisms behind their up-regulation are not entirely understood. The cleaved form of the Notch1 protein, intracellular Notch1 (N1(IC)), is involved in transcriptional regulation of genes. To test whether Notch1 is involved in the expression of multidrug resistance-associated protein 1 (ABCC1/MRP1; herein referred to as ABCC1), we measured N1(IC) and presenilin 1 (PSEN1), the catalytic subunit of γ-secretase required for Notch activation. We observed higher levels of N1(IC) and PSEN1 proteins as well as higher activity of N1(IC) in ABCC1-expressing MDR MCF7/VP cells compared with parental MCF7/WT cells. Reducing N1(IC) levels in MCF7/VP cells with either a γ-secretase inhibitor or shRNA led to reduction of ABCC1. By contrast, ectopic expression of N1(IC) in MCF7/WT cells led to increased expression of ABCC1 and associated drug resistance, consistent with expression of this transporter. Inhibition of ABCC1 reversed drug resistance of N1(IC)-overexpressing stable cells. Using an ABCC1 promoter construct, we observed both its reduced transcriptional activity after blocking the generation of N1(IC) and its increased transcriptional activity in stable cells overexpressing N1(IC). ChIP and gel-shift assays revealed an interaction between a specific promoter region of ABCC1 and the N1(IC)-activated transcription factor CBF1, suggesting that the regulation of ABCC1 expression by Notch1 is mediated by CBF1. Indeed, deletion or site-directed mutagenesis of these CBF1 binding sites within the ABCC1 promoter region attenuated promoter-reporter activity. Overall, our results reveal a unique regulatory mechanism of ABCC1 expression.
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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.