ArticleScientific reports2018
Dysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Anastellin: A Fibronectin-Derived Peptide Targeting the Tumor Microenvironment Through ECM Modulation.Cell biochemistry and biophysics · 2026Review
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression.British journal of cancer · 2024Article
- Liver X Receptors Enhance Epithelial to Mesenchymal Transition in Metastatic Prostate Cancer Cells.Cancers · 2024Article
- Versatile Design of Organic Polymeric Nanoparticles for Photodynamic Therapy of Prostate Cancer.ACS materials Au · 2024Review
- Mutations F352A and Y528A in human HSP90α reduce fibronectin association and fibrillogenesis in cell-derived matrices.Cell stress & chaperones · 2023Article
- Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.Cancers · 2023Article
- Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer.British journal of cancer · 2023Article
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Advancements in Oncoproteomics Technologies: Treading toward Translation into Clinical Practice.Proteomes · 2023Review
- Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.Cells · 2023Article
- Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants.Cancers · 2022Article
- Article
- AlphaFold predicted structure of the Hsp90-like domains of the neurodegeneration linked protein sacsin reveals key residues for ATPase activity.Frontiers in molecular biosciences · 2022Article
- Prognostic model and immunotherapy prediction based on molecular chaperone-related lncRNAs in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Article
- Predicting Bone Metastasis Using Gene Expression-Based Machine Learning Models.Frontiers in genetics · 2021Article
- Article
- Fibronectin in Cancer: Friend or Foe.Cells · 2019Review
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment. Validation in PCa cell lines revealed that AUY922 caused marked alterations to cell morphology, and suppressed cell motility and invasion compared to vehicle or 17-AAG, concomitant with dysregulation of key extracellular matrix proteins such as fibronectin (FN1). Interestingly, while the expression of FN1 was increased by AUY922, FN1 secretion was significantly decreased. This resulted in cytosolic accumulation of FN1 protein within late endosomes, suggesting that AUY922 disrupts vesicular secretory trafficking pathways. Depletion of FN1 by siRNA knockdown markedly reduced the invasive capacity of PCa cells, phenocopying AUY922. These results highlight a novel mechanism of action for AUY922 beyond its established effects on cellular mitosis and survival and, furthermore, identifies extracellular matrix cargo delivery as a potential therapeutic target for the treatment of aggressive PCa.
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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.