ArticleNature communications2021
Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82 citing papers in PubMed, 128 citations in OpenAlex.
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- Metabolic Checkpoints in Cutaneous Squamous Cell Carcinoma: ACSL1 and PPARD Orchestrate Lipid-Ferroptosis Crosstalk via Keratinocyte Remodeling.Applied biochemistry and biotechnology · 2026Article
- Unveiling Lipid Metabolism-Related Gene PTGDS: A Tumor Suppressor in Lung Adenocarcinoma with Therapeutic Potential.Cancers · 2026Article
- Disrupting SOX2 self-association and condensate formation to overcome chemotherapeutic drug resistance in lung squamous cell carcinoma.Signal transduction and targeted therapy · 2026Article
- Aneuploidy sensitizes cells to SREBP-pathway inhibition in squamous cell carcinoma.bioRxiv : the preprint server for biology · 2026Article
- PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.Autophagy · 2026Article
- Gomisin B promotes RSL3-induced ferroptosis in neuroblastoma by inhibiting the ESR1/USP7/SREBF1 axis.Cell biology and toxicology · 2026Article
- Review
- Environmental Lead Promotes Breast Cancer Migration and Invasion via the AKR1C3-NF-κB-MMP Axis.Biomedicines · 2026Article
- Mast cell driven immunometabolism as a therapeutic entry point in ESCC.Frontiers in cell and developmental biology · 2026Review
- SF3B4 stabilizes SREBF1 via 3'UTR binding to drive hepatocellular carcinoma progression.Frontiers in oncology · 2026Article
- Acetyl-CoA carboxylase 1 knockdown promotes esophageal squamous cell carcinoma metastasis via the CXCL8-NET axis.Communications biology · 2025Article
- Insulin signalling-associated cell fate promotes neoplastic invasiveness in non-functioning pituitary gonadotroph adenoma via cis-regulatory elements activation.British journal of cancer · 2025Article
- RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness.Journal of experimental & clinical cancer research : CR · 2025Article
- Imidacloprid contributes to bladder cancer progression: preliminary evidence based on network toxicology, machine learning and molecular docking.BMC pharmacology & toxicology · 2025Article
- Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma.World journal of clinical oncology · 2025Article
- Ferroptosis-related hub genes and immune cell dynamics as diagnostic biomarkers in age-related macular degeneration.European journal of medical research · 2025Article
- Identification of the putative regulatory regions and candidate genes associated with backfat thickness and intramuscular fat content traits in Xiang pigs.BMC genomics · 2025Article
- Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment.Biomedicines · 2025Review
- Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease.Brain, behavior, & immunity - health · 2025Article
22 more citing papers are in PubMed but not listed here.
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23 authors at 6 institutions in 4 countries.
Funding
Abstract
Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.
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