ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Targeting Squalene Epoxidase Confers Metabolic Vulnerability and Overcomes Chemoresistance in HNSCC.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Evaluating cholesterol de novo synthesis biomarkers: a systematic review and meta-analysis of cancer prognosis and clinical outcomes.BMC cancer · 2025Pooled it
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Metabolic-epigenetic reprogrammingActa pharmaceutica Sinica. B · 2026Article
- Simvastatin Restores Cisplatin Sensitivity by Suppressing the Caveolin-1-Mediated PI3K/AKT Signaling Pathway in Cisplatin-Resistant Cervical Cancer Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- Cholesterol synthases suppress metastasis and stemness through PDIA4/ACLY or SYVN1/SCD1 axis in advanced colorectal cancer.Communications biology · 2026Article
- OCIAD2 Stabilizes Integrin β1 Signaling Through SNX17-Mediated Endosomal Recycling to Lipid Rafts and Modulates Cisplatin Response in HNSCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Functional characterization of 2,3-oxidosqualene cyclase8 in Taraxacum mongolicum: overexpression enhances taraxasterol biosynthesis and antioxidant capacity.BMC genomics · 2026Article
- Metabolomic and transcriptomic profiling of HNSCC identifies AMIGO2 as a therapeutic target modulating tumor microenvironment.NPJ precision oncology · 2025Article
- METTL1-driven epitranscriptomic enhancement of TXNDC12 boosts c-Myc stability through USP5 in HNSCC.Experimental & molecular medicine · 2025Article
- PRMT1-Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- CK2α-mediated phosphorylation of DUB3 promotes YAP1 stability and oncogenic functions.Cell death & disease · 2025Article
- The role of the tumor microenvironment in HNSCC resistance and targeted therapy.Frontiers in immunology · 2025Review
- Development and Validation of a Cholesterol-related Gene Signature for Prognostic Assessment in Head and Neck Squamous Cell Carcinoma.Current medicinal chemistry · 2025Article
- Advances in the study of posttranslational modifications of histones in head and neck squamous cell carcinoma.Clinical epigenetics · 2024Review
- Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment.Cell death & disease · 2024Review
- Article
- New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases.Journal of nanobiotechnology · 2024Review
- Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway.Journal of experimental & clinical cancer research : CR · 2024Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Cisplatin resistance poses a substantial hurdle in effectively treating head and neck squamous cell carcinoma (HNSCC). Utilizing multiple tumor models and examining an internal HNSCC cohort, squalene epoxidase (SQLE) is pinpointed as a key driver of chemoresistance and tumorigenesis, operating through a cholesterol-dependent pathway. Comprehensive transcriptomic analysis reveals that SQLE is essential for maintaining c-Myc transcriptional activity by stabilizing the c-Myc protein and averting its ubiquitin-mediated degradation. Mechanistic investigation demonstrates that SQLE inhibition diminishes Akt's binding affinity to lipid rafts via a cholesterol-dependent process, subsequently deactivating lipid raft-localized Akt, reducing GSK-3β phosphorylation at S9, and increasing c-Myc phosphorylation at T58, ultimately leading to c-Myc destabilization. Importantly, employing an Sqle conditional knockout mouse model, SQLE's critical role in HNSCC initiation and progression is established. The preclinical findings demonstrate the potent synergistic effects of combining terbinafine and cisplatin in arresting tumor growth. These discoveries not only provide novel insights into the underlying mechanisms of SQLE-mediated cisplatin resistance and tumorigenesis in HNSCC but also propose a promising therapeutic avenue for HNSCC patients unresponsive to conventional cisplatin-based chemotherapy.
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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.