ArticleFrontiers in oncology2021
Heat Shock Protein 90 Triggers Multi-Drug Resistance of Ovarian Cancer via AKT/GSK3β/β-Catenin Signaling.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Identification of novel drug-specific PARP inhibitor resistance mechanisms in ovarian cancer-implications for clinical practice.British journal of cancer · 2026Article
- Vernodalin andBiomedicines · 2026Article
- HSP90β as a potential prognostic biomarker in urothelial carcinoma: insights from NF-κB, IL-8, and heat-shock protein expression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis.Frontiers in pharmacology · 2026Article
- Divergent oncogenic signaling and immune microenvironment changes in low-grade serous ovarian cancer patients undergoing intraperitoneal chemotherapy.NPJ precision oncology · 2025Article
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Upregulation of MMP3 Promotes Cisplatin Resistance in Ovarian Cancer.International journal of molecular sciences · 2025Article
- Vorinostat impairs the cancer-driving potential of leukemia-secreted extracellular vesicles.Journal of translational medicine · 2025Article
- A new weapon: the application of tumor vaccines based on extracellular exosomal heat shock proteins in immunotherapy.Frontiers in immunology · 2025Review
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones' Antimalignancy Properties.International journal of molecular sciences · 2024Article
- Review
- Modulation of Heat Shock Protein Expression in Alveolar Adenocarcinoma Cells through Gold Nanoparticles and Cisplatin Treatment.Pharmaceutics · 2024Article
- Investigating the role of HSP90 in cancer cell phenotypic plasticity.Journal of breast cancer research · 2024Article
- Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.Cell death & disease · 2023Article
- Overexpression of HSPB6 inhibits osteosarcoma progress through the ERK signaling pathway.Clinical and experimental medicine · 2023Article
- Cross-Linking Mass Spectrometry on P-Glycoprotein.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the most lethal gynaecologic tumor, with which multi-drug resistance as the major therapeutic hindrance. Heat shock protein 90 (Hsp90) has been involved in cancer malignant behaviors. However, its role and mechanism in multi-drug resistance of ovarian cancer remains poorly understood. Our results demonstrated that Hsp90 was overexpressed in multi-drug resistant ovarian cancer cells. Hsp90 downregulation by shHsp90 or inhibitor BIIB021 increased the sensitivity of multi-drug resistant ovarian cancer cells to paclitaxel and cisplatin, and augmented the drugs-induced apoptosis. Hsp90 positively regulated the expressions of multi-drug resistance protein 1 (P-gp/MDR1), breast cancer resistance protein (BCRP), Survivin and Bcl-2 expressions closely associated with multi-drug resistance. Moreover, overexpression of Hsp90 promoted β-catenin accumulation, while Hsp90 downregulation decreased the accumulation, nuclear translocation and transcriptional activity of β-catenin. We also identified that β-catenin was responsible for Hsp90-mediated expressions of P-gp, BCRP, Survivin, and Bcl-2. Furthermore, Hsp90 enhanced the AKT/GSK3β signaling, and AKT signaling played a critical role in Hsp90-induced accumulation and transcriptional activity of β-catenin, as well as multi-drug resistance to paclitaxel and cisplatin. In conclusion, Hsp90 enhanced the AKT/GSK3β/β-catenin signaling to induce multi-drug resistance of ovarian cancer. Suppressing Hsp90 chemosensitized multi-drug resistant ovarian cancer cells via impairing the AKT/GSK3β/β-catenin signaling, providing a promising therapeutic strategy for a successful treatment of ovarian cancer.
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