ArticleNature communications2021
FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.Nature cancer · 2026Article
- Targeted inhibition of FBXL2 confers susceptibility of HER2-negative breast cancer to trastuzumab deruxtecan.Nature cancer · 2026Article
- Nebivolol Inhibits Hepatocellular Carcinoma via RHOQ and Enhances the Efficacy of Lenvatinib.International journal of biological sciences · 2026Article
- Diversified, endothelial cell-dependent cancer cell response to hypertensive serum modified by antihypertensive drugs.Scientific reports · 2025Article
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Activating NEDD4L suppresses EGFR-driven lung adenocarcinoma growth via facilitating EGFR proteasomal degradation.Journal of experimental & clinical cancer research : CR · 2025Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- AI662270/GRP94 axis couples the unfolded protein response to mitochondrial dynamics during acute myocardial infarction.JCI insight · 2025Article
- DEPTOR suppresses lymphomagenesis by promoting EGFR degradation via HUWE1 E3 ligase.Cell death and differentiation · 2025Article
- Targeting the SYVN1-EGFR axis: a breakthrough strategy for TKI-resistant NSCLC.Cell death & disease · 2025Article
- VDR Decrease Enhances the Efficacy of 1,25-Dihydroxyvitamin D3 Inhibiting Gefitinib Resistance by Regulating EGFR/FASN Loop in NSCLC Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Maize leaf yellowing gene ZmCAAX modulates growth and drought resistance by regulating abscisic acid contents through interaction with the ABA biosynthetic enzyme ZmNCED3.Plant biotechnology journal · 2025Article
- Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.Acta pharmaceutica Sinica. B · 2025Article
- Molecular mechanisms of phytoconstituents from selected Egyptian plants against non-small cell lung cancer using integrated in vitro network pharmacology and molecular docking approach.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Scutellarin mitigates high glucose-induced pyroptosis in diabetic atherosclerosis: Role of Nrf2-FBXL2-mediated NLRP3 degradation.Endocrine journal · 2025Article
- A novel USP4 inhibitor that suppresses colorectal cancer stemness by promoting β-catenin and Twist1 degradation.Journal of translational medicine · 2025Article
- pSTAT3 transactivates EGFR in maintaining EGFR protein homeostasis and EGFR-TKI resistance.Acta biochimica et biophysica Sinica · 2024Article
- CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer.Cell death discovery · 2024Article
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
Corrections and comments
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Authors and funding
30 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore, we show that glucose-regulated protein 94 (Grp94) protects EGFR from degradation via blockage of FBXL2 binding to EGFR. Moreover, we have identified nebivolol, a clinically used small molecule inhibitor, that can upregulate FBXL2 expression to inhibit EGFR-driven NSCLC growth. Nebivolol in combination with osimertinib or Grp94-inhibitor-1 exhibits strong inhibitory effects on osimertinib-resistant NSCLC. Together, this study demonstrates that the FBXL2-Grp94-EGFR axis plays a critical role in NSCLC development and suggests that targeting FBXL2-Grp94 to destabilize EGFR may represent a putative therapeutic strategy for TKI-resistant NSCLC.
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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.