ArticleNature communications2021
An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Loss of p53-DREAM-mediated repression of cell cycle genes as a driver of lymph node metastasis in head and neck cancer.Genome medicine · 2023Pooled it
- TRIM28 Increases RFC4 Protein Expression to Promote Triple-Negative Breast Cancer Progression.MedComm · 2026Article
- ZNF200 and DDX17 regulatory loop promotes tumor growth and metastasis by activating RBPJ transcription in non-small cell lung cancer.Science China. Life sciences · 2026Article
- Association between the TP63 and CIR1 polymorphisms and non-small cell lung cancer in Chinese population.Journal of cardiothoracic surgery · 2026Article
- DLL1-mediated ferroptosis resistance via the Notch-Nrf2/GPX4 axis drives cisplatin resistance in ovarian cancer.Cancer & metabolism · 2026Article
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy.Nature communications · 2026Article
- Notch1 O-GlcNAcylation drives tumor stemness and mechanoadaptation to a stiff microenvironment and promotes chordoma recurrence.The Journal of clinical investigation · 2026Article
- BEX2 influences the MCL1-Hedgehog signaling axis to regulate the potential of stemness characterization in colorectal cancer.Cancer biology & medicine · 2026Article
- Leveraging proteomics and machine learning for mechanism and biomarker discovery on glioma progression and transformation: from LGG to GBM.Human genomics · 2026Article
- PRKD1/EIF5A/β-catenin axis inhibits tumorigenesis and metastasis in non-small-cell lung cancer.Clinical and experimental medicine · 2026Article
- Gut microbiota drives cancer evolution and therapy resistance.Molecular cancer · 2026Review
- TAF1 acetyltransferase promotes colorectal carcinoma metastasis by catalyzing β-hydroxybutyrylation of KCTD9.Oncogene · 2026Article
- Multiple roles of replication factor C family in pan‑cancer (Review).Oncology reports · 2025Review
- β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer.Cancer biology & therapy · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Aberrant Notch-signaling promotes tumor angiogenesis in esophageal squamous-cell carcinoma.Signal transduction and targeted therapy · 2025Article
- Porous PLGA microspheres for the inhalation delivery of icariin and miR-23b in the treatment of metastatic lung cancer.Asian journal of pharmaceutical sciences · 2025Article
- Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.
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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.