ArticleScientific reports2018
Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Discovery of a Novel Small-Molecule Modulator for Full-length YB-1 Protein via Integrated Computational and in vitro Biophysical Approaches.Applied biochemistry and biotechnology · 2026Article
- Fisetin: a multitarget flavonol bridging oxidative stress, inflammation, aging, and cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Deciphering the cancer chemopreventive potential of phytochemicals: an integrative perspective on molecular targets and signaling networks.Cancer cell international · 2026Review
- Integrative Investigation of Flavonoids Targeting YBX1 Protein-Protein Interaction Network in Breast Cancer: From Computational Analysis to Experimental Validation.Molecular biotechnology · 2025Article
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- Overexpressed RPS6KA1 and its potential diagnostic value in head and neck squamous cell carcinoma.Discover oncology · 2025Article
- Targeting SIRT1: A Potential Strategy for Combating Severe COVID-19.BioMed research international · 2025Review
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Y-Box Binding Protein 1: Unraveling the Multifaceted Role in Cancer Development and Therapeutic Potential.International journal of molecular sciences · 2024Review
- YB-1 activating cascades as potential targets in KRAS-mutated tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells.Cells · 2023Article
- YB-1 Expression Is Associated with Lymph Node Metastasis and Drug Resistance to Adriamycin in Breast Cancer.Disease markers · 2023Article
- Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
- ERK/RSK-mediated phosphorylation of Y-box binding protein-1 aggravates diabetic cardiomyopathy by suppressing its interaction with deubiquitinase OTUB1.The Journal of biological chemistry · 2022Article
- RNA-binding proteins and their role in kidney disease.Nature reviews. Nephrology · 2022Review
- An old friend with a new face: YB-1 and its role in healthy pregnancy and pregnancy-associated complications.Frontiers in cell and developmental biology · 2022Article
- A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance.Cellular signalling · 2021Review
- Review
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The anti-proliferative activity of dietary flavonoid fisetin has been validated in various cancer models. Establishing its precise mechanism of action has proved somewhat challenging given the multiplicity of its targets. We demonstrated that YB-1 promotes epithelial-to-mesenchymal transition and its inhibition suppressed tumor cell proliferation and invasion. The p90 ribosomal S6 kinase (RSK), an important ERK effector, activates YB-1 to drive melanoma growth. We found that fisetin treatment of monolayer/3-D melanoma cultures resulted in YB-1 dephosphorylation and reduced transcript levels. In parallel, fisetin suppressed mesenchymal markers and matrix-metalloproteinases in melanoma cells. Data from cell-free/cell-based systems indicated that fisetin inhibited RSK activity through binding to the kinase. Affinity studies for RSK isoforms evaluated stronger interaction for RSK2 than RSK1. Competition assays performed to monitor binding responses revealed that YB-1 and RSK2 do not compete, rather binding of fisetin to RSK2 promotes its binding to YB-1. Fisetin suppressed YB-1/RSK signaling independent of its effect on ERK, and reduced MDR1 levels. Comparable efficacy of fisetin and vemurafenib for inhibiting melanoma growth was noted albeit through divergent modulation of ERK. Our studies provide insight into additional modes of regulation through which fisetin interferes with melanoma growth underscoring its potential therapeutic efficacy in disease progression.
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