ArticleMolecular cancer research : MCR2021
The Hippo Pathway Effector YAP Promotes Ferroptosis via the E3 Ligase SKP2.
Article in Molecular cancer research : MCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Ferroptosis in glioma treatment: Current situation, prospects and drug applications.Frontiers in oncology · 2022Pooled it
- The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer.The Prostate · 2021Trial
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- A HRH1-YAP1 feedback loop drives pancreatic cancer progression and predicts therapeutic response.Oncology letters · 2026Article
- TROP2 confers resistance to oxidative stress-induced cancer cell death through YAP/HMOX1 signaling.Journal of translational medicine · 2026Article
- LBPs NPs suppress breast cancer progression by inhibiting YAP1 expression to induce ferroptosis and alter energy metabolism.Scientific reports · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Yes-associated protein 1 in cancer: bridging mechanical transduction and epigenetic regulation.Cancer biology & therapy · 2025Review
- Ferroptosis-Mediated Cell-Specific Damage: Molecular Cascades and Therapeutic Breakthroughs in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2025Review
- Chr:17q21.31 locus risk haplotype H1 susceptibility to ferroptosis is mediated by endolysosomal pathway.Cell death & disease · 2025Article
- Ferroptosis and non-coding RNAs in lung cancer: exploring molecular mechanisms and diagnostic/therapeutic implications.Cancer cell international · 2025Review
- Activated Hippo Pathway is Associated with a Worse Response to Trastuzumab and Worse Survival in HER2-Positive Breast Cancer.Annals of surgical oncology · 2025Article
- Mechanotransduction-related ferroptosis: Enhancing boron neutron capture therapy efficacy in glioblastoma using a spheroid model.Molecular therapy. Oncology · 2025Article
- Carnitine Shuttle and Ferroptosis in Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage.Diabetes & metabolism journal · 2025Article
- KLF9, Epigenetic Silenced by DNMT1, Promotes ERK-Mediated Ferroptosis of Osteoarthritic Chondrocytes Through Transcriptionally Regulating CYP1B1.Journal of cellular and molecular medicine · 2025Article
- Review
- Enhanced ferroptosis sensitivity promotes the formation of highly myopic cataract via the DDR2-Hippo pathway.Cell death & disease · 2025Article
- Important molecular mechanisms in ferroptosis.Molecular and cellular biochemistry · 2025Review
- Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.iScience · 2025Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Ferroptosis is a new form of regulated cell death resulting from the accumulation of lipid-reactive oxygen species. A growing number of studies indicate ferroptosis as an important tumor suppressor mechanism having therapeutic potential in cancers. Previously, we identified TAZ, a Hippo pathway effector, regulates ferroptosis in renal and ovarian cancer cells. Because YAP (Yes-associated protein 1) is the one and only paralog of TAZ, sharing high sequence similarity and functional redundancy with TAZ, we tested the potential roles of YAP in regulating ferroptosis. Here, we provide experimental evidence that YAP removal confers ferroptosis resistance, whereas overexpression of YAP sensitizes cancer cells to ferroptosis. Furthermore, integrative analysis of transcriptome reveals S-phase kinase-associated protein 2 (SKP2), an E3 ubiquitin ligase, as a YAP direct target gene that regulates ferroptosis. We found that the YAP knockdown represses the expression of SKP2. Importantly, the genetic and chemical inhibitions of SKP2 robustly protect cells from ferroptosis. In addition, knockdown of YAP or SKP2 abolishes the lipid peroxidation during erastin-induced ferroptosis. Collectively, our results indicate that YAP, similar to TAZ, is a determinant of ferroptosis through regulating the expression of SKP2. Therefore, our results support the connection between Hippo pathway effectors and ferroptosis with significant therapeutic implications. IMPLICATIONS: This study reveals that YAP promotes ferroptosis by regulating SKP2, suggesting novel therapeutic options for YAP-driven tumors.
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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.