ArticleACS chemical biology2015
Hsp90 C-terminal inhibitors exhibit antimigratory activity by disrupting the Hsp90α/Aha1 complex in PC3-MM2 cells.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 37 citations in OpenAlex.
- Trial
- AHSA1 promotes the progression of lung cancer by enhancing the expression of HSP90α.Histology and histopathology · 2026Article
- Extracellular heat shock protein 90 alpha (eHsp90α)'s role in cancer progression and the development of therapeutic strategies.European journal of medicinal chemistry · 2024Review
- miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia.Scientific reports · 2024Article
- The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.Cancers · 2024Review
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Recent advances toward the development of Hsp90 C-terminal inhibitors.Bioorganic & medicinal chemistry letters · 2023Review
- Regulation of Protein Transport Pathways by the Cytosolic Hsp90s.Biomolecules · 2022Review
- Diagnostic value of HSP90α and related markers in lung cancer.Journal of clinical laboratory analysis · 2022Article
- Synthesis and Evaluation of Small Molecule Disruptors of the Aha1/Hsp90 Complex for the Reduction of Tau Aggregation.ACS medicinal chemistry letters · 2022Article
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- The Prognostic and Immunotherapeutic Significance of AHSA1 in Pan-Cancer, and Its Relationship With the Proliferation and Metastasis of Hepatocellular Carcinoma.Frontiers in immunology · 2022Article
- Co-chaperones TIMP2 and AHA1 Competitively Regulate Extracellular HSP90:Client MMP2 Activity and Matrix Proteolysis.Cell reports · 2019Article
- Inhibitors and chemical probes for molecular chaperone networks.The Journal of biological chemistry · 2019Review
- Extracellular Hsp90α clinically correlates with tumor malignancy and promotes migration and invasion in esophageal squamous cell carcinoma.OncoTargets and therapy · 2019Article
- Rac1 activation links tau hyperphosphorylation and Aβ dysmetabolism in Alzheimer's disease.Acta neuropathologica communications · 2018Article
- Heat shock protein 90: its inhibition and function.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Hsp90 activator Aha1 drives production of pathological tau aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hsp90 inhibitors radicicol and geldanamycin have opposing effects on Leishmania Aha1-dependent proliferation.Cell stress & chaperones · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human Hsp90 isoforms are molecular chaperones that are often up-regulated in malignances and represent a primary target for Hsp90 inhibitors undergoing clinical evaluation. Hsp90α is a stress-inducible isoform of Hsp90 that plays a significant role in apoptosis and metastasis. Though Hsp90α is secreted into the extracellular space under metastatic conditions, its role in cancer biology is poorly understood. We report that Hsp90α associates with the Aha1 co-chaperone and found this complex to localize in secretory vesicles and at the leading edge of migrating cells. Knockdown of Hsp90α resulted in a defect in cell migration. The functional role of Hsp90α/Aha1 was studied by treating the cells with various novobiocin-based Hsp90 C-terminal inhibitors. These inhibitors disrupted the Hsp90α/Aha1 complex, caused a cytoplasmic redistribution of Hsp90α and Aha1, and decreased cell migration. Structure-function studies determined that disruption of Hsp90α/Aha1 association and inhibition of cell migration correlated with the presence of a benzamide side chain, since an acetamide substituted analog was less effective. Our results show that disruption of Hsp90α/Aha1 interactions with novobiocin-based Hsp90 C-terminal inhibitors may limit the metastatic potential of tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.