ArticleMolecular oncology2020
Novel C-terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self-renewal, and epithelial-mesenchymal transition.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 papers.
What it found
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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
13 citing papers in PubMed, 19 citations in OpenAlex.
- CancerHubs: a systematic data mining and elaboration approach for identifying novel cancer-related protein interaction hubs.Briefings in bioinformatics · 2024Article
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- circSLC4A7 accelerates stemness and progression of gastric cancer by interacting with HSP90 to activate NOTCH1 signaling pathway.Cell death & disease · 2023Article
- TRPA1 activation and Hsp90 inhibition synergistically downregulate macrophage activation and inflammatory responses in vitro.BMC immunology · 2023Article
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy.International journal of molecular sciences · 2022Review
- Maggot Extract Inhibits Cell Migration and Tumor Growth by Targeting HSP90AB1 in Ovarian Cancer.Journal of clinical medicine · 2022Article
- Combination of AURKA inhibitor and HSP90 inhibitor to treat breast cancer with AURKA overexpression and TP53 mutations.Medical oncology (Northwood, London, England) · 2022Review
- A novel HSP90 inhibitor SL-145 suppresses metastatic triple-negative breast cancer without triggering the heat shock response.Oncogene · 2022Article
- A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas.Melanoma research · 2021Article
- SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway.Journal of Cancer · 2021Article
- Nanosized Drug Delivery Systems for Breast Cancer Stem Cell Targeting.International journal of nanomedicine · 2021Review
- 17-AAG Induces Endoplasmic Reticulum Stress-mediated Apoptosis in Breast Cancer Cells, Possibly Through PERK/eIF2α Up-regulation.In vivo (Athens, Greece)Article
Corrections and comments
- Retracted
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
In patients with triple-negative breast cancer (TNBC), evidence suggests that tumor-initiating cells (TIC) have stem cell-like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational maintenance of many client proteins in TIC development. Therefore, we hypothesize that the novel C-terminal HSP90 inhibitors KU711 and KU758 can target TIC and represent a promising strategy for overcoming metastasis. Human breast cancer cells (MDA-MB-468LN, MDA-MB-231) treated with the HSP90 inhibitors KU711, KU758, and 17-AAG showed a 50-80% decrease in TIC markers CD44 and aldehyde dehydrogenase (P < 0.01) as assessed by flow cytometry. A decrease in sphere formation, which was used to assess self-renewal, was observed after the treatment of TNBC cells starting at 2.5 µm KU711 and 0.31 µm KU758. KU compounds also blocked the invasion and migration of TNBC cells in a dose-dependent manner. The knockdown of HSP90 clients was observed without any change in prosurvival HSP70 levels. In vivo, in a murine orthotopic breast cancer model, treatment with KU758 and KU711 yielded an approximately twofold and a fourfold reduction in tumor volumes versus control, respectively, without demonstrated toxicity. In conclusion, C-terminal HSP90 inhibitors are potent novel therapeutics against TNBC in vitro and in vivo as they target TICs and block invasion, EMT transition, and self-renewal.
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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 Socratic graph.