ArticleNature communications2023
Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- An EZH2-SREBP2 axis promotes cholesterol biosynthesis and represents a noncanonical vulnerability in tumorigenesis.Nature cell biology · 2026Article
- Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.Cell death & disease · 2026Article
- Obesity and diabetes associated with dysregulation of mevalonate pathway markers and progression from pancreatic intraepithelial neoplasia to invasive pancreatic tumor.Stem cell research & therapy · 2026Article
- Self-fueling catalysis-driven membrane destabilization triggers CSC-enriched tumors ablation.Journal of nanobiotechnology · 2026Article
- NAT10 promotes gallbladder cancer progression by remodeling cholesterol metabolism via PCSK9 mRNA acetylation.Cell death discovery · 2026Article
- APC coordinates GSK3 phosphorylation of SETD8 to suppress colorectal cancer.Cell reports · 2026Article
- Interplay Between Gut Microbiota and Cholesterol Metabolism in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Targeting fibroblast derived thrombospondin 2 disrupts an immune-exclusionary environment at the tumor front in colorectal cancer.Nature communications · 2025Article
- The Wnt/APC destruction complex targets SREBP2 in a β-catenin-independent pathway to control cholesterol metabolism.bioRxiv : the preprint server for biology · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- PMA exerts anti-leukemia effect in PhCancer cell international · 2025Article
- Single-Cell Dissection of the Serrated Pathway: Cellular Heterogeneity and Genetic Causality in Colorectal Cancer.International journal of molecular sciences · 2025Article
- Making sense of human colorectal cancer molecular subtypes: mice are stepping in.Cell death discovery · 2025Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- RNASET2 Deficiency Induces Hepatocellular Carcinoma Metastasis through Cholesterol-Triggered MET Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies.Chinese medical journal · 2025Review
- FASN promotes the stemness of cancer stem cells and protects colorectal cancer cells from ferroptosis by inhibiting the activation of SREBP2.Frontiers in immunology · 2025Article
- FBXW7/GSK3β-mediated proline-rich 11 degradation promotes oxidative DNA damage and inhibits tumor progression in renal cell carcinoma.Theranostics · 2025Article
- SREBP2 as a central player in cancer progression: potential for targeted therapeutics.Frontiers in pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 8 institutions in 4 countries.
Funding
Abstract
The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.
Indexed as
Identifiers
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.