ArticleNature communications2018
Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Notch2, a Key Player in Chronic Lymphocytic Leukemia: Mechanism, Microenvironment Interactions, and Therapeutic Implications.Cancers · 2026Review
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Sex hormone receptor signaling networks drive pancreatic solid-pseudopapillary neoplasm pathogenesis and therapy.Discover oncology · 2025Review
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells.Cancer cell international · 2024Article
- Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Journal of hematology & oncology · 2024Review
- Progression of Notch signaling regulation of B cells under radiation exposure.Frontiers in immunology · 2024Review
- Identification of the Axis β-Catenin-BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment.International journal of molecular sciences · 2023Article
- Circular RNAs: implications of signaling pathways and bioinformatics in human cancer.Cancer biology & medicine · 2023Review
- Cadherins and catenins in cancer: connecting cancer pathways and tumor microenvironment.Frontiers in cell and developmental biology · 2023Review
- To β or Not to β: How Important Is β-Catenin Dependent and Independent WNT Signaling in CLL?Cancers · 2022Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- hiPSC-derived bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukemia.Cell reports. Medicine · 2022Article
- Immunoglobulin Gene Sequence as an Inherited and Acquired Risk Factor for Chronic Lymphocytic Leukemia.Cancers · 2022Review
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 9 institutions in 2 countries.
Funding
Abstract
The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells. Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL cells, which interacts with and further stabilises β-catenin. Together, these stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs microenvironment-mediated survival of tumour cells. Similarly, inhibition of Notch signalling diminishes survival of stroma-protected CLL cells in vitro and disease engraftment in vivo. Notch2 activation in the microenvironment is a pre-requisite for the activation of canonical Wnt signalling in tumour cells.
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Registered trials
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.