ArticleOncogene2017
Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 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
50 citing papers in PubMed, 76 citations in OpenAlex.
- Rearrangement of the Cell Chaperone Machinery in Human Fibrosarcoma HT1080 Cells With the Knocked-Out HSP90AA1 Gene Encoding Hsp90α.Biology of the cell · 2026Article
- Activated Platelet-Released Heat Shock Protein 90α Triggers Autophagy-Dependent Neutrophil Extracellular Trap Formation and Amplifies Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- The value of plasma levels of heat shock protein 90α for predicting the treatment efficacy and prognosis of lung cancer.Discover oncology · 2026Article
- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
- Review
- Development and evaluation of Hsp90-targeting nanobodies for visualisation of extracellular Hsp90 in tumours using PET imaging.EJNMMI radiopharmacy and chemistry · 2025Article
- A nomogram based on plasma HSP90α and NLR for predicting prognosis in advanced gastric cancer patients treated with PD-1 inhibitors.Journal of Cancer · 2025Article
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- Extracellular heat shock protein 90 alpha (eHsp90α)'s role in cancer progression and the development of therapeutic strategies.European journal of medicinal chemistry · 2024Review
- Article
- Review
- Identification of immunogenic cell death-related genes involved in Alzheimer's disease.Scientific reports · 2024Article
- Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.Cell death & disease · 2023Article
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Synthesis and Validation of the First Cell-Impermeable Hsp90α-Selective Inhibitors.ACS medicinal chemistry letters · 2023Article
- Review
- Endometriosis Stem Cells as a Possible Main Target for Carcinogenesis of Endometriosis-Associated Ovarian Cancer (EAOC).Cancers · 2022Review
- HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling.Journal for immunotherapy of cancer · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and β) have been shown to support tumour progression. The tumour-supporting activity of the intracellular Hsp90 is attributed to their N-terminal ATPase-driven chaperone function. What molecular entity determines the extracellular function of secreted Hsp90 and the distinction between Hsp90α and Hsp90β was unclear. Here we demonstrate that CRISPR/Case9 knocking out Hsp90α nullifies tumour cells' ability to migrate, invade and metastasize without affecting the cell survival and growth. Knocking out Hsp90β leads to tumour cell death. Extracellular supplementation with recombinant Hsp90α, but not Hsp90β, protein recovers tumourigenicity of the Hsp90α-knockout cells. Sequential mutagenesis identifies two evolutionarily conserved lysine residues, lys-270 and lys-277, in the Hsp90α subfamily that determine the extracellular Hsp90α function. Hsp90β subfamily lacks the dual lysine motif and the extracellular function. Substitutions of gly-262 and thr-269 in Hsp90β with lysines convert Hsp90β to a Hsp90α-like protein. Newly constructed monoclonal antibody, 1G6-D7, against the dual lysine region of secreted Hsp90α inhibits both de novo tumour formation and expansion of already formed tumours in mice. This study suggests an alternative therapeutic approach to target Hsp90 in cancer, that is, the tumour-secreted Hsp90α, instead of the intracellular Hsp90α and Hsp90β.
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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.