ArticleMolecular cell2012
EGFR-induced and PKCε monoubiquitylation-dependent NF-κB activation upregulates PKM2 expression and promotes tumorigenesis.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 153 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
153 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
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- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- Role of elevation of glycolysis in tumor-associated macrophages in glioblastoma immune evasion and therapeutic implications.PNAS nexus · 2026Review
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- The Pivotal Role of NF-κB in Glioblastoma: Mechanisms of Activation and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Nucleus-translocated glucokinase functions as a protein kinase to phosphorylate TAZ and promote tumour growth.Nature communications · 2025Article
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- The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression.Frontiers in bioscience (Landmark edition) · 2025Review
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
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- Exosomal long non-coding RNA-LINC00839 promotes lung adenocarcinoma progression by activating NF-κB signaling pathway.Annals of medicine · 2024Article
- Hexosaminidase B-driven cancer cell-macrophage co-dependency promotes glycolysis addiction and tumorigenesis in glioblastoma.Nature communications · 2024Article
- Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets.Cells · 2024Review
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Many types of human tumor cells have overexpressed pyruvate kinase M2 (PKM2). However, the mechanism underlying this increased PKM2 expression remains to be defined. We demonstrate here that EGFR activation induces PLCγ1-dependent PKCε monoubiquitylation at Lys321 mediated by RINCK1 ubiquitin ligase. Monoubiquitylated PKCε interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKCε phosphorylates IKKβ at Ser177 and activates IKKβ. Activated RelA interacts with HIF1α, which is required for RelA to bind the PKM promoter. PKCε- and NF-κB-dependent PKM2 upregulation is required for EGFR-promoted glycolysis and tumorigenesis. In addition, PKM2 expression correlates with EGFR and IKKβ activity in human glioblastoma specimens and with grade of glioma malignancy. These findings highlight the distinct regulation of NF-κB by EGF, in contrast to TNF-α, and the importance of the metabolic cooperation between the EGFR and NF-κB pathways in PKM2 upregulation and tumorigenesis.
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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.