ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Super-Enhancer Driven LIF/LIFR-STAT3-SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- USP14 promotes head and neck squamous cell carcinoma progression via deubiquitinating and stabilizing CFL2.Future science OA · 2026Article
- ALKBH5 in Cancer-Associated Fibroblasts Governs an Epitranscriptomic Axis That Drives Pancreatic Cancer Metastasis.Cancer research · 2026Article
- Effect of xeroderma pigmentosum group C on the characteristics and regulatory mechanisms of lung cancer stem cells.International journal of oncology · 2026Article
- ANKRD28 interacts with DOCK180 to activate Rac1-STAT3-Myc signaling and sustain stemness of CD34Molecular and cellular biochemistry · 2026Article
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- A Non-Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Leukemia inhibitory factor drives malignant progression in lung squamous cell carcinoma via the PI3K/AKT/GSK-3β/β-catenin axis.Journal of molecular histology · 2026Article
- A human patient-derived organoid biobank to model tumor heterogeneity and therapeutic vulnerability for oral squamous cell carcinoma.Cell reports. Medicine · 2026Article
- KIF20A inhibits TRIM21-dependent ubiquitination of DHX9 to boost SOX2 stability, enhancing OSCC stemness and ferroptosis resistance.Cell death & disease · 2026Article
- Patient-derived orthotopic xenograft models recapitulate the peritoneal dissemination of pancreatic cancer and delineate its transcriptional and regulatory programs.Journal of experimental & clinical cancer research : CR · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Fezf2 regulates differentiation of Aire-expressing and post-Aire mimetic epithelial populations maintaining thymic homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Targeting the LHX1-LDB1 Complex Restores STING-dependent Senescence Surveillance and Inhibits Head and Neck Cancer Progression.International journal of biological sciences · 2026Article
- A novel super-enhancer-driven lncRNA LINC00973 governs head and neck squamous cell carcinoma progression through EN2.Cell death & disease · 2025Article
- AI-driven multi-omics integration of cancer-associated fibroblasts for prognostic modeling and therapeutic target discovery in head and neck squamous cell carcinoma.NPJ precision oncology · 2025Article
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- DUSP3 restrains the progression and stemness property of osteosarcoma through regulating EGFR/STAT3/SOX2 axis.International journal of biological sciences · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Super-enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identify leukemia inhibitory factor (LIF)-SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer-associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine/paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF-SE recruit SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activates downstream LIFR-STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF-SE-LIF/LIFR-STAT3-SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlate with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma dramatically diminish following cancer eradication. Therapeutically, pharmacological targeting LIF-SE-LIF/LIFR-STAT3 significantly impairs tumor growth and reduces CSC subpopulations in xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF-SE-mediated auto-regulatory loop in regulating HNSCC stemness and highlight LIF as a novel noninvasive biomarker and potential therapeutic target for HNSCC.
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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.