ArticleThe EMBO journal2021
PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 64 citations in OpenAlex.
- E2F1-mediated transcriptional regulation of TMEM33 promotes colorectal cancer proliferation, metastasis, and EMT.Human cell · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- TMEM33 regulates the proliferation and migration of lung adenocarcinoma by promoting the PI3K/AKT/mTOR signaling pathway.Cancer cell international · 2026Article
- Trichostatin A Influences Dendritic Cells' Functions by Regulating Glucose and Lipid Metabolism via PKM2.Molecules (Basel, Switzerland) · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- TMEM33 deletion potentiates anti-tumor CD8bioRxiv : the preprint server for biology · 2026Article
- PKM2 is the Metabolic Checkpoint for Stemness Features in Head and Neck Cancer.Journal of Cancer · 2026Article
- Sesamin attenuates atherosclerosis by alleviating vascular endothelial ferroptosis-related injuryFrontiers in cell and developmental biology · 2026Article
- The deubiquitinating enzyme UCHL3 promotes bladder cancer progression and glycolysis through enhancing PKM2 protein stability.Frontiers in oncology · 2026Article
- The endo-lysosomal-lipid axis: bidirectional interactions between membrane trafficking dysfunction and lipid metabolic disorders.Frontiers in cell and developmental biology · 2026Review
- PKM2 is a key regulator of cardiac lipid metabolism in mice.Mitochondrion · 2025Article
- Deletion of C3G in hepatocytes impairs full liver maturation and alters glucose homeostasis.Cell death & disease · 2025Article
- Exosomal PKM2: A Noninvasive Diagnostic Marker Linking Macrophage Metabolic Reprogramming to Gastric Cancer Pathogenesis.Cancer science · 2025Article
- Article
- PKM2 knockout facilitates the activation of the AMPK/KLF4/ACADVL pathway, leading to increased oxidative degradation of fatty acids in TNBC.Medical oncology (Northwood, London, England) · 2025Article
- HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The emerging role of transmembrane proteins in tumorigenesis and therapy.Translational cancer research · 2025Review
- The TRPV1-PKM2-SREBP1 axis maintains microglial lipid homeostasis in Alzheimer's disease.Cell death & disease · 2025Article
- MTX2 facilitates PKM2 tetramerization to promote cardiac glucose metabolism and protects the heart against ischemia/reperfusion injury.Theranostics · 2025Article
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
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14 authors at 1 institution in 1 country.
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Abstract
The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer cells to regulate anabolic metabolism. Although PKM2 was recently reported to regulate lipid homeostasis, the molecular mechanism remains unclear. Herein, we discovered an ER transmembrane protein 33 (TMEM33) as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism. Loss of PKM2 leads to up-regulation of TMEM33, which recruits RNF5, an E3 ligase, to promote SREBP-cleavage activating protein (SCAP) degradation. TMEM33 is transcriptionally regulated by nuclear factor erythroid 2-like 1 (NRF1), whose cleavage and activation are controlled by PKM2 levels. Total plasma cholesterol levels are elevated by either treatment with PKM2 tetramer-promoting agent TEPP-46 or by global PKM2 knockout in mice, highlighting the essential function of PKM2 in lipid metabolism. Although depletion of PKM2 decreases cancer cell growth, global PKM2 knockout accelerates allografted tumor growth. Together, our findings reveal the cell-autonomous and systemic effects of PKM2 in lipid homeostasis and carcinogenesis, as well as TMEM33 as a bona fide regulator of lipid metabolism.
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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.