ArticleThe Journal of biological chemistry2018
Nitric oxide promotes cancer cell dedifferentiation by disrupting an Oct4:caveolin-1 complex: A new regulatory mechanism for cancer stem cell formation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Loss of long-range co-expression is a common feature in cancer.NPJ systems biology and applications · 2026Article
- Cytoplasmic p21 promotes stemness of colon cancer cells via activation of the NFκB pathway.Molecular oncology · 2026Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer.Biomolecules · 2025Article
- The neuroepithelial origin of ovarian carcinomas explained through an epithelial-mesenchymal-ectodermal transition enhanced by cisplatin.Scientific reports · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- The critical roles of caveolin-1 in lung diseases.Frontiers in pharmacology · 2024Review
- Targeting Nitric Oxide: Say NO to Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Research trends and hotspots on the links between caveolin and cancer: bibliometric and visual analysis from 2003 to 2022.Frontiers in pharmacology · 2023Article
- Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity.Advances in cancer research · 2023Review
- Redox-Regulation in Cancer Stem Cells.Biomedicines · 2022Review
- Endothelial nitric oxide synthase (eNOS)-NO signaling axis functions to promote the growth of prostate cancer stem-like cells.Stem cell research & therapy · 2022Article
- [Lung Cancer Stem-like Cells and Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Regulation of Tumor and Metastasis Initiation by Chemokine Receptors.Journal of Cancer · 2022Review
- HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions.Journal of Cancer · 2022Article
- Caveolin1: its roles in normal and cancer stem cells.Journal of cancer research and clinical oncology · 2021Review
- Protein Phosphorylation in Cancer: Role of Nitric Oxide Signaling Pathway.Biomolecules · 2021Review
- Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology.Antioxidants (Basel, Switzerland) · 2021Review
- Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs.International journal of molecular sciences · 2021Review
- The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review.International journal of stem cells · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) are unique populations of cells that can self-renew and generate different cancer cell lineages. Although CSCs are believed to be a promising target for novel therapies, the specific mechanisms by which these putative therapeutics could intervene are less clear. Nitric oxide (NO) is a biological mediator frequently up-regulated in tumors and has been linked to cancer aggressiveness. Here, we search for targets of NO that could explain its activity. We find that it directly affects the stability and function of octamer-binding transcription factor 4 (Oct4), known to drive the stemness of lung cancer cells. We demonstrated that NO promotes the CSC-regulatory activity of Oct4 through a mechanism that involves complex formation between Oct4 and the scaffolding protein caveolin-1 (Cav-1). In the absence of NO, Oct4 forms a molecular complex with Cav-1, which promotes the ubiquitin-mediated proteasomal degradation of Oct4. NO promotes Akt-dependent phosphorylation of Cav-1 at tyrosine 14, disrupting the Cav-1:Oct4 complex. Site-directed mutagenesis and computational modeling studies revealed that the hydroxyl moiety at tyrosine 14 of Cav-1 is crucial for its interaction with Oct4. Both removal of the hydroxyl via mutation to phenylalanine and phosphorylation lead to an increase in binding free energy (Δ
Indexed as
Identifiers
What OpenQuestion holds
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.