ArticleOncogene2016
Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.
Article in Oncogene, 2016. 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 34 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- PKM2 Deficiency Results in Reduced Proliferation of Nasopharyngeal Carcinoma Cells by Deactivation of Nrf2-HO-1-GSH Signaling.Applied biochemistry and biotechnology · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- From description to prediction: a multi-database bibliometric forecast-validation study of lung cancer and tumor-associated macrophages research (2005-2025).Frontiers in immunology · 2026Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Review
- β-lapachone suppresses carcinogenesis of cervical cancer via interaction with AKT1.Frontiers in pharmacology · 2025Article
- Role of pyruvate kinase M2 in regulating sepsis (Review).Molecular medicine reports · 2024Review
- Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis-Related Metabolic Enzymes in the Cytoplasm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.Nature communications · 2024Article
- Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer.Scientific reports · 2024Article
- Article
- An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1.British journal of cancer · 2023Article
- Long noncoding RNAs: glycolysis regulators in gynaecologic cancers.Cancer cell international · 2023Review
- A small-molecule compound D6 overcomes EGFR-T790M-mediated resistance in non-small cell lung cancer.Communications biology · 2021Article
- HELZ2 promotes K63-linked polyubiquitination of c-Myc to induce retinoblastoma tumorigenesis.Medical oncology (Northwood, London, England) · 2021Article
- Article
- PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia.Cancers · 2021Article
- Article
- HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.PLoS biology · 2021Article
- Glycolysis-induced drug resistance in tumors-A response to danger signals?Neoplasia (New York, N.Y.) · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secondary mutation of epidermal growth factor receptor (EGFR) resulting in drug resistance is one of the most critical issues in lung cancer therapy. Several drugs are being developed to overcome EGFR tyrosine kinase inhibitor (TKI) resistance. Here, we report that pyruvate kinase M2 (PKM2) stabilized mutant EGFR protein by direct interaction and sustained cell survival signaling in lung cancer cells. PKM2 silencing resulted in markedly reduced mutant EGFR expression in TKI-sensitive or -resistant human lung cancer cells, and in inhibition of tumor growth in their xenografts, concomitant with downregulation of EGFR-related signaling. Mechanistically, PKM2 directly interacted with mutant EGFR and heat-shock protein 90 (HSP90), and thus stabilized EGFR by maintaining its binding with HSP90 and co-chaperones. Stabilization of EGFR relied on dimeric PKM2, and the protein half-life of mutant EGFR decreased when PKM2 was forced into its tetramer form. Clinical levels of PKM2 positively correlated with mutant EGFR expression and with patient outcome. These results reveal a previously undescribed non-glycolysis function of PKM2 in the cytoplasm, which contribute to EGFR-dependent tumorigenesis and provide a novel strategy to overcome drug resistance to EGFR TKIs.
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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.