ArticleNature communications2024
The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 19 citations in OpenAlex.
- Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy.Cancer medicine · 2026Review
- LPCAT3 is essential for leukemia progression and represents a therapeutic vulnerability in AML.Blood science (Baltimore, Md.) · 2026Article
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Targeting USP10/SCD1 axis by RAF265 suppresses lipogenesis and induced ferroptosis in head and neck squamous cell carcinoma.Cell death discovery · 2026Article
- Targeting C5AR1 disrupts complement-driven G0-phase maintenance and overcomes metabolic drug resistance in glioma.Journal of translational medicine · 2026Article
- Review
- Dysregulation of Aurora Kinases andCurrent issues in molecular biology · 2026Article
- HPV16 E7 Enhances Cell Stemness via RTKN2-Mediated Activation of the NF-κB Pathway in Cervical Cancer.Biochemical genetics · 2026Article
- Effects of Wnt10a on dentinogenesis of dental pulp cells in a 3-dimensional culture system using atelocollagen gel.Odontology · 2026Article
- E2F1-Driven WDHD1 Transcription Enhances Cell-Cycle Progression and Promotes Pancreatic Cancer Progression.Current oncology (Toronto, Ont.) · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Characterization of pancreatic cancer stem cells and construction of a stem cell-based prognostic signature.Scientific reports · 2025Article
- E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.Journal of experimental & clinical cancer research : CR · 2025Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery.International journal of molecular sciences · 2025Review
- DSG2 promotes pancreatic cancer stem cell maintenance via support of tumour and macrophage cellular cross-talk.Cell death & disease · 2025Article
- Prunin: An Emerging Anticancer Flavonoid.International journal of molecular sciences · 2025Review
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Pancreatic Cancer Immunotherapy: A Team-Based Approach.Cancer treatment and research · 2025Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways and cell-autonomous transcriptional machinery orchestrate the stem cell-like characteristics of CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins of CSCs in pancreatic cancer. We uncover that the cell-autonomous E2F1/4-pRb/RBL2 axis balances non-cell-autonomous signalling in healthy ductal cells but becomes deregulated upon KRAS mutation. E2F1 and E2F4 induce whereas pRb/RBL2 reduce WNT ligand expression (e.g. WNT7A, WNT7B, WNT10A, WNT4) thereby regulating self-renewal, chemoresistance and invasiveness of CSCs in both PDAC and breast cancer, and fibroblast proliferation. Screening for epigenetic enzymes identifies GCN5 as a regulator of CSCs that deposits H3K9ac onto WNT promoters and enhancers. Collectively, paracrine signalling pathways are controlled by the E2F-GCN5-RB axis in diverse cancers and this could be a therapeutic target for eliminating CSCs.
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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.