ArticleOncotarget2015
Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- HDAC6 modulates the cognitive behavioral function and hippocampal tissue pathological changes of APP/PS1 transgenic mice through HSP90-HSF1 pathway.Experimental brain research · 2024Article
- HSP90 Exacerbates Bone Destruction in Rheumatoid Arthritis by Activating TRAF6/NFATc1 Signaling.Inflammation · 2024Article
- The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.Cancers · 2024Review
- The small-molecule drug homoharringtonine targets HSF1 to suppress pancreatic cancer progression.American journal of cancer research · 2024Article
- Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology.Cancers · 2023Review
- Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia.Medical oncology (Northwood, London, England) · 2023Article
- Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.Theranostics · 2023Review
- Harnessing the power of traditional Chinese medicine monomers and compound prescriptions to boost cancer immunotherapy.Frontiers in immunology · 2023Review
- HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation.Frontiers in immunology · 2023Review
- HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia.Nature communications · 2022Article
- Clinical significance and potential mechanism of heat shock factor 1 in acute myeloid leukemia.Aging · 2022Article
- Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia.Cancers · 2021Article
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- Anti-oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient-derived tumor xenograft model.Head & neck · 2019Article
- Small Molecule Inhibitors of HSF1-Activated Pathways as Potential Next-Generation Anticancer Therapeutics.Molecules (Basel, Switzerland) · 2018Review
- Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells.Oncotarget · 2018Article
- Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.PLoS genetics · 2018Article
- Triptolide suppresses the in vitro and in vivo growth of lung cancer cells by targeting hyaluronan-CD44/RHAMM signaling.Oncotarget · 2017Article
- Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression.Current genomics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
CLL is a disease characterized by chromosomal deletions, acquired copy number changes and aneuploidy. Recent studies have shown that overexpression of Heat Shock Factor (HSF) 1 in aneuploid tumor cells can overcome deficiencies in heat shock protein (HSP) 90-mediated protein folding and restore protein homeostasis. Interestingly, several independent studies have demonstrated that HSF1 expression and activity also affects the chaperoning of HSP90 kinase clients, although the mechanism underlying this observation is unclear. Here, we determined how HSF1 regulates HSP90 function using CLL as a model system. We report that HSF1 is overexpressed in CLL and treatment with triptolide (a small molecule inhibitor of HSF1) induces apoptosis in cultured and primary CLL B-cells. We demonstrate that knockdown of HSF1 or its inhibition with triptolide results in the reduced association of HSP90 with its kinase co-chaperone cell division cycle 37 (CDC37), leading to the partial depletion of HSP90 client kinases, Bruton's Tyrosine Kinase (BTK), c-RAF and cyclin-dependent kinase 4 (CDK4). Treatment with triptolide or HSF1 knockdown disrupts the cytosolic complex between HSF1, p97, HSP90 and the HSP90 deacetylase- Histone deacetylase 6 (HDAC6). Consequently, HSF1 inhibition results in HSP90 acetylation and abrogation of its chaperone function. Finally, tail vein injection of Mec-1 cells into Rag2-/-IL2Rγc-/- mice followed by treatment with minnelide (a pro-drug of triptolide), reduced leukemia, increased survival and attenuated HSP90-dependent survival signaling in vivo. In conclusion, our study provides a strong rationale to target HSF1 and test the activity of minnelide against human CLL.
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.