ArticleBlood2010
Heat shock protein 90 regulates the expression of Wilms tumor 1 protein in myeloid leukemias.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
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- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
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- Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.NPJ breast cancer · 2022Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- lncRNAMolecular therapy. Nucleic acids · 2021Article
- The tumor suppressor miR-642a-5p targets Wilms Tumor 1 gene and cell-cycle progression in prostate cancer.Scientific reports · 2021Article
- WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.Journal of translational medicine · 2020Article
- Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma.Journal of cellular and molecular medicine · 2020Article
- CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia.Investigational new drugs · 2019Article
- Wilms' tumor 1 drives fibroproliferation and myofibroblast transformation in severe fibrotic lung disease.JCI insight · 2018Article
- Cross Talk between Radiation and Immunotherapy: The Twain Shall Meet.Radiation research · 2018Review
- Article
- Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia.Haematologica · 2016Review
- The targeted histone deacetylase inhibitor tefinostat (CHR-2845) shows selective in vitro efficacy in monocytoid-lineage leukaemias.Oncotarget · 2016Article
- Review
- HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer.Oncogene · 2014Article
- WTAP is a novel oncogenic protein in acute myeloid leukemia.Leukemia · 2014Article
- The transcription factor Wilms tumor 1 confers resistance in myeloid leukemia cells against the proapoptotic therapeutic agent TRAIL (tumor necrosis factor α-related apoptosis-inducing ligand) by regulating the antiapoptotic protein Bcl-xL.The Journal of biological chemistry · 2012Article
- Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
The aberrant overexpression of Wilms tumor 1 (WT1) in myeloid leukemia plays an important role in blast cell survival and resistance to chemotherapy. High expression of WT1 is also associated with relapse and shortened disease-free survival in patients. However, the mechanisms by which WT1 expression is regulated in leukemia remain unclear. Here, we report that heat shock protein 90 (Hsp90), which plays a critical role in the folding and maturation of several oncogenic proteins, associates with WT1 protein and stabilizes its expression. Pharmacologic inhibition of Hsp90 resulted in ubiquitination and subsequent proteasome-dependant degradation of WT1. RNAi-mediated silencing of WT1 reduced the survival of leukemia cells and increased the sensitivity of these cells to chemotherapy and Hsp90 inhibition. Furthermore, Hsp90 inhibitors 17-AAG [17-(allylamino)-17-demethoxygeldanamycin] and STA-9090 significantly reduced the growth of myeloid leukemia xenografts in vivo and effectively down-regulated the expression of WT1 and its downstream target proteins, c-Myc and Bcl-2. Collectively, our studies identify WT1 as a novel Hsp90 client and support the crucial role for the WT1-Hsp90 interaction in maintaining leukemia cell survival. These findings have significant implications for developing effective therapies for myeloid leukemias and offer a strategy to inhibit the oncogenic functions of WT1 by clinically available Hsp90 inhibitors.
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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.