ArticleProceedings of the National Academy of Sciences of the United States of America2008
Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
- Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.Chemical science · 2025Article
- HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.Cell death and differentiation · 2023Article
- Senescent cells: A therapeutic target for osteoporosis.Cell proliferation · 2022Review
- The Heat Shock Protein 90 (HSP90) Is Required for the IL-33-Induced Cytokine Production in Mast Cells (MCs).International journal of molecular sciences · 2022Article
- Studies on Streptomyces sp. SN-593: reveromycin biosynthesis, β-carboline biomediator activating LuxR family regulator, and construction of terpenoid biosynthetic platform.The Journal of antibiotics · 2022Review
- 3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche.Scientific reports · 2021Article
- Review
- Attenuation of SRC Kinase Activity Augments PARP Inhibitor-mediated Synthetic Lethality inClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Role of the heat shock protein family in bone metabolism.Cell stress & chaperones · 2018Review
- Mitochondria on the move: emerging paradigms of organelle trafficking in tumour plasticity and metastasis.British journal of cancer · 2017Review
- Acetylation of androgen receptor by ARD1 promotes dissociation from HSP90 complex and prostate tumorigenesis.Oncotarget · 2016Article
- Article
- Chemical and biological studies of reveromycin A.The Journal of antibiotics · 2016Review
- Identification of Middle Chain Fatty Acyl-CoA Ligase Responsible for the Biosynthesis of 2-Alkylmalonyl-CoAs for Polyketide Extender Unit.The Journal of biological chemistry · 2015Article
- 5-Azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival.The Journal of biological chemistry · 2015Article
- Article
- Low dose Hsp90 inhibitor 17AAG protects neural progenitor cells from ischemia induced death.Journal of cell communication and signaling · 2014Article
- Structure-function analyses of cytochrome P450revI involved in reveromycin A biosynthesis and evaluation of the biological activity of its substrate, reveromycin T.The Journal of biological chemistry · 2014Article
- Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.
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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.