ArticleThe Journal of biological chemistry2011
Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 97 citations in OpenAlex.
- 5-O-Methylvisammioside alleviates depression-like behaviors by inhibiting nuclear factor kappa B pathway activation via targeting SRC.Neural regeneration research · 2026Article
- Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.Cancers · 2026Review
- Emerging Frontiers in Neuro-Oncology: Insights into Extracellular Vesicle-Driven Tumor Mechanisms and Nanotherapeutic Strategies.International journal of molecular sciences · 2025Review
- Targeting proteostasis pathways for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Retraction: Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between capillary cells.Oncotarget · 2025Article
- Role of Innate Immunity in Cancer.Advances in experimental medicine and biology · 2025Review
- Fetuin-A Modulates Tumor Growth and Invasion in a Basal-like Triple Negative Breast Cancer Cell line, MDA-MB-468.Journal of pharmacy and pharmacology research · 2025Article
- Extracellular heat shock protein 90 alpha (eHsp90α)'s role in cancer progression and the development of therapeutic strategies.European journal of medicinal chemistry · 2024Review
- Article
- Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer.International journal of molecular sciences · 2022Article
- Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells.Cellular and molecular life sciences : CMLS · 2022Article
- Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma.Journal of hematology & oncology · 2021Review
- [Neuregulin 2 is highly expressed in glioma tissues to regulate glial fibrillary acidic protein expressionNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- The dark-side of the outside: how extracellular heat shock proteins promote cancer.Cellular and molecular life sciences : CMLS · 2021Review
- Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression.Frontiers in cell and developmental biology · 2021Review
- Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy.Frontiers in endocrinology · 2021Review
- Modulation of Pathological Pain by Epidermal Growth Factor Receptor.Frontiers in pharmacology · 2021Review
- Neuregulin 1 enhances cell adhesion molecule L1 like expression levels and promotes malignancy in human glioma.Oncology letters · 2020Article
- A 2,5-Dihydroxybenzoic Acid-Gelatin Conjugate Inhibits the Basal and Hsp90-Stimulated Migration and Invasion of Tumor Cells.Journal of functional biomaterials · 2020Article
- TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme-Future Perspectives.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular heat shock protein HSP90α was reported to participate in tumor cell growth, invasion, and metastasis formation through poorly understood signaling pathways. Herein, we show that extracellular HSP90α favors cell migration of glioblastoma U87 cells. More specifically, externally applied HSP90α rapidly induced endocytosis of EGFR. This response was accompanied by a transient increase in cytosolic Ca(2+) appearing after 1-3 min of treatment. In the presence of EGF, U87 cells showed HSP90α-induced Ca(2+) oscillations, which were reduced by the ATP/ADPase, apyrase, and inhibited by the purinergic P(2) inhibitor, suramin, suggesting that ATP release is requested. Disruption of lipid rafts with methyl β-cyclodextrin impaired the Ca(2+) rise induced by extracellular HSP90α combined with EGF. Specific inhibition of TLR4 expression by blocking antibodies suppressed extracellular HSP90α-induced Ca(2+) signaling and the associated cell migration. HSPs are known to bind lipopolysaccharides (LPSs). Preincubating cells with Polymyxin B, a potent LPS inhibitor, partially abrogated the effects of HSP90α without affecting Ca(2+) oscillations observed with EGF. Extracellular HSP90α induced EGFR phosphorylation at Tyr-1068, and this event was prevented by both the protein kinase Cδ inhibitor, rottlerin, and the c-Src inhibitor, PP2. Altogether, our results suggest that extracellular HSP90α transactivates EGFR/ErbB1 through TLR4 and a PKCδ/c-Src pathway, which induces ATP release and cytosolic Ca(2+) increase and finally favors cell migration. This mechanism could account for the deleterious effects of HSPs on high grade glioma when released into the tumor cell microenvironment.
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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.