ArticleNature cell biology2015
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 140 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- Histological and Genetic Markers of Cellular Senescence in Keratinocyte Cancers and Actinic Keratosis: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- The real-world efficacy and safety of anlotinib in advanced non-small cell lung cancer.Journal of cancer research and clinical oncology · 2022Trial
- Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial.JAMA oncology · 2018Trial
- A TERRA-NONO axis drives fibroblast reprogramming in cancer.Science advances · 2026Article
- Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches.Immunity · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Comments on "Dual-layer spectral detector CT-based scoring system for noninvasive TP53 expression assessment and adjuvant chemotherapy response prediction in gastric cancer: a multicenter cross-sectional study".International journal of surgery (London, England) · 2026Article
- Nanomedicine for targeting cancer-associated fibroblasts in cancer therapy.Theranostics · 2026Review
- Development and validation of a CAF-related signature for prognosis and therapy response in colorectal cancer: new insights on HSPB1.NPJ precision oncology · 2025Article
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- ATG7-deficient fibroblast promotes breast cancer progression via exosome-mediated downregulation of SCARB1.Cell death & disease · 2025Article
- KAT7 contributes to ponatinib-induced hypertension by promoting endothelial senescence and inflammatory responses through activating NF-κB signaling pathway.Journal of hypertension · 2025Article
- Cancer-Associated Fibroblasts as the "Architect" of the Lung Cancer Immune Microenvironment: Multidimensional Roles and Synergistic Regulation with Radiotherapy.International journal of molecular sciences · 2025Review
- Tumor suppressor genes in the tumor microenvironment.Disease models & mechanisms · 2025Review
- Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities.Nature reviews. Cancer · 2025Review
- Immune therapeutic strategies for the senescent tumor microenvironment.British journal of cancer · 2025Review
- The solid tumor microenvironment and related targeting strategies: a concise review.Frontiers in immunology · 2025Review
- Revisiting the role of cancer-associated fibroblasts in tumor microenvironment.Frontiers in immunology · 2025Review
- Oncogenic GALNT5 confers FOLFIRINOX resistance via activating the MYH9/ NOTCH/ DDR axis in pancreatic ductal adenocarcinoma.Cell death & disease · 2024Article
- The expression of RBPJ and its potential role in rheumatoid arthritis.BMC genomics · 2024Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Stromal fibroblast senescence has been linked to ageing-associated cancer risk. However, density and proliferation of cancer-associated fibroblasts (CAFs) are frequently increased. Loss or downmodulation of the Notch effector CSL (also known as RBP-Jκ) in dermal fibroblasts is sufficient for CAF activation and ensuing keratinocyte-derived tumours. We report that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as a direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is downmodulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas, whereas p53 expression and function are downmodulated only in the latter, with paracrine FGF signalling as the probable culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effectors and promotes stromal and cancer cell expansion. The findings support a CAF activation-stromal co-evolution model under convergent CSL-p53 control.
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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.