ArticleOncogene2016
Cancer stem cell drugs target K-ras signaling in a stemness context.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
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
55 citing papers in PubMed, 91 citations in OpenAlex.
- From Phytotoxin to Cell-Death Probe: Ophiobolin A and Related Sesterterpenoids in Membrane Stress and Non-Apoptotic Cell Death.Molecules (Basel, Switzerland) · 2026Review
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Chrono-Pharmacology for Cancer: Harnessing Circadian Regulations of the Cell Cycle and Immune Response Dynamics for Precision Therapy.ACS pharmacology & translational science · 2025Review
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.Bioorganic & medicinal chemistry letters · 2025Article
- An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.Molecular diversity · 2024Review
- SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers.Nature communications · 2024Article
- Therapeutic vulnerabilities of cancer stem cells and effects of natural products.Natural product reports · 2023Review
- K-Ras Binds Calmodulin-Related Centrin1 with Potential Implications for K-Ras Driven Cancer Cell Stemness.Cancers · 2023Article
- A Stereoselective Photoinduced Cycloisomerization Inspired by Ophiobolin A.Organic letters · 2022Article
- A Modeling and Analysis Study Reveals That CaMKII in Synaptic Plasticity Is a Dominant Affecter in CaM Systems in a T286 Phosphorylation-Dependent Manner.Molecules (Basel, Switzerland) · 2022Article
- ARL2 is required for homologous recombination repair and colon cancer stem cell survival.FEBS open bio · 2022Article
- Rapid Access to Ironomycin Derivatives by Click Chemistry.ACS organic & inorganic Au · 2022Article
- Bruceine D Identified as a Drug Candidate against Breast Cancer by a Novel Drug Selection Pipeline and Cell Viability Assay.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A DFT/PCM Study on the Affinity of Salinomycin to Bind Monovalent Metal Cations.Molecules (Basel, Switzerland) · 2022Article
- Potential of phenothiazines to synergistically block calmodulin and reactivate PP2A in cancer cells.PloS one · 2022Article
- Development of a High-throughput NanoBRET Screening Platform to Identify Modulators of the RAS/RAF Interaction.Molecular cancer therapeutics · 2021Article
- Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Elaiophylin Is a Potent Hsp90/ Cdc37 Protein Interface Inhibitor with K-Ras Nanocluster Selectivity.Biomolecules · 2021Article
- Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. Salinomycin is the most established CSC inhibitor. However, its primary mechanistic target is still unclear, impeding the discovery of compounds with similar anti-CSC activity. Here, we show that salinomycin very specifically interferes with the activity of K-ras4B, but not H-ras, by disrupting its nanoscale membrane organization. We found that caveolae negatively regulate the sensitivity to this drug. On the basis of this novel mechanistic insight, we defined a K-ras-associated and stem cell-derived gene expression signature that predicts the drug response of cancer cells to salinomycin. Consistent with therapy resistance of CSC, 8% of tumor samples in the TCGA-database displayed our signature and were associated with a significantly higher mortality. Using our K-ras-specific screening platform, we identified several new candidate CSC drugs. Two of these, ophiobolin A and conglobatin A, possessed a similar or higher potency than salinomycin. Finally, we established that the most potent compound, ophiobolin A, exerts its K-ras4B-specific activity through inactivation of calmodulin. Our data suggest that specific interference with the K-ras4B/calmodulin interaction selectively inhibits CSC.
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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.