ArticleNature metabolism2022
Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 120 citations in OpenAlex.
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- Exploring regulated cell death in renal cell carcinoma: mechanistic insights and therapeutic perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Every-Other-Day Fasting Prehabilitation Attenuates Secondary Injury Following Spinal Cord Injury and Is Associated with Stage-Dependent SREBP1-Related Metabolic-Immune Remodeling.Molecular neurobiology · 2026Article
- Association ofGenes · 2026Article
- The transcription factor ZNF217 drives hepatocellular carcinoma progression by activating de novo lipid synthesis via FASN upregulation.Journal of cancer research and clinical oncology · 2026Article
- A risk stratification framework based on ammonia-induced cell death signatures for prognostic assessment and therapeutic insights in colorectal cancer.Discover oncology · 2026Article
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- ABCC2 as a novel therapeutic target in lung adenocarcinoma: a machine learning-driven discovery linking ammonia metabolism to prognosis and drug resistance.Journal of translational medicine · 2026Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- SREBP1-activated lipid metabolism drives ferroptosis and progression of clear cell renal cell carcinoma.Science China. Life sciences · 2026Article
- Effects of dietary glutamine supplementation on lipid metabolism, fatty acid composition, and taste properties in the longissimus thoracis muscle of feed-restricted yaks.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Article
- Prognostic and immunological roles of ammonia-induced cell death-related genes in non-small cell lung cancer.BMC pulmonary medicine · 2026Article
- A Supramolecular Nanoscavengers: Based "Cargo-Exchange" Breaking Cholesterol Metabolic Dysregulation for Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer.EMBO reports · 2026Article
- Ammonia signaling network: the intersection of tumor metabolism, epigenetics, and metastasis.Frontiers in endocrinology · 2026Review
- Fermented Milk as an Alternative Therapy for Obesity.International journal of food science · 2026Review
- Acidosis and the role of nanotechnology in mitigating cancer progression.Oncology reviews · 2026Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Tumorigenesis is associated with elevated glucose and glutamine consumption, but how cancer cells can sense their levels to activate lipid synthesis is unknown. Here, we reveal that ammonia, released from glutamine, promotes lipogenesis via activation of sterol regulatory element-binding proteins (SREBPs), endoplasmic reticulum-bound transcription factors that play a central role in lipid metabolism. Ammonia activates the dissociation of glucose-regulated, N-glycosylated SREBP-cleavage-activating protein (SCAP) from insulin-inducible gene protein (Insig), an endoplasmic reticulum-retention protein, leading to SREBP translocation and lipogenic gene expression. Notably, 25-hydroxycholesterol blocks ammonia to access its binding site on SCAP. Mutating aspartate D428 to alanine prevents ammonia binding to SCAP, abolishes SREBP-1 activation and suppresses tumour growth. Our study characterizes the unknown role, opposite to sterols, of ammonia as a key activator that stimulates SCAP-Insig dissociation and SREBP-1 activation to promote tumour growth and demonstrates that SCAP is a critical sensor of glutamine, glucose and sterol levels to precisely control lipid synthesis.
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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.