ArticleOncogene2009
Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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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
63 citing papers in PubMed, 134 citations in OpenAlex.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.Cancers · 2024Review
- Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinomaFrontiers in oncology · 2024Article
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- Inhibition of Cdc37 Ameliorates Arthritis in Collagen-Induced Arthritis Rats by Inhibiting Synoviocyte Proliferation and Migration Through the ERK Pathway.Inflammation · 2023Article
- Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90.Scientific reports · 2021Article
- Novel Small Molecule Hsp90/Cdc37 Interface Inhibitors Indirectly Target K-Ras-Signaling.Cancers · 2021Article
- Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions.Cell stress & chaperones · 2021Review
- CDC37L1 acts as a suppressor of migration and proliferation in gastric cancer by down-regulating CDK6.Journal of Cancer · 2021Article
- The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37.International journal of molecular sciences · 2020Article
- Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2.Carcinogenesis · 2020Article
- MiR-302 Regulates Glycolysis to Control Cell-Cycle during Neural Tube Closure.International journal of molecular sciences · 2020Article
- Structure, Function, and Regulation of the Hsp90 Machinery.Cold Spring Harbor perspectives in biology · 2019Review
- Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer.Science advances · 2019Article
- Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer.Cancer science · 2018Article
- Up-Regulation of Cdc37 Contributes to Schwann Cell Proliferation and Migration After Sciatic Nerve Crush.Neurochemical research · 2018Article
- Targeting the Hsp90-Cdc37-client protein interaction to disrupt Hsp90 chaperone machinery.Journal of hematology & oncology · 2018Review
- Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells.FEBS open bio · 2018Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The cochaperone CDC37 promotes the association of HSP90 with the protein kinase subset of client proteins to maintain their stability and signalling functions. HSP90 inhibitors induce depletion of clients, which include several oncogenic kinases. We hypothesized that the targeting of CDC37 using siRNAs would compromise the maturation of these clients and increase the sensitivity of cancer cells to HSP90 inhibitors. Here, we show that silencing of CDC37 in human colon cancer cells diminished the association of kinase clients with HSP90 and reduced levels of the clients ERBB2, CRAF, CDK4 and CDK6, as well as phosphorylated AKT. CDC37 silencing promoted the proteasome-mediated degradation of kinase clients, suggesting a degradation pathway independent from HSP90 binding. Decreased cell signalling through kinase clients was also demonstrated by reduced phosphorylation of downstream substrates and colon cancer cell proliferation was subsequently reduced by the inhibition of the G1/S-phase transition. Furthermore, combining CDC37 silencing with the HSP90 inhibitor 17-AAG induced more extensive and sustained depletion of kinase clients and potentiated cell cycle arrest and apoptosis. These results support an essential role for CDC37 in concert with HSP90 in maintaining oncogenic protein kinase clients and endorse the therapeutic potential of targeting CDC37 in cancer.
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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.