ArticleJournal of experimental & clinical cancer research : CR2018
HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
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201 citing papers in PubMed, 298 citations in OpenAlex.
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- <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑κB signaling pathway with Hsp90 as a potential biomarker</p>.Molecular medicine reports · 2026Article
- Single-Cell Analysis Reveals Epithelial Heterogeneity and Tumor Microenvironment Characteristics During the Malignant Progression of Colorectal Cancer.Biomedicines · 2026Article
- Emerging research themes in drug resistance in osteosarcoma: a 25-year bibliometric and visualized analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- HSP90AA1-VDAC1 interaction contributes to breast cancer progression and doxorubicin resistance through PI3K/AKT signaling.Breast cancer research : BCR · 2026Article
- METTL3-mediated mMolecular cancer · 2026Article
- HSP90AA1 restrains clear cell renal cell carcinoma progression by promoting CADM1 expression and suppressing the PI3K-AKT pathway through interaction with FBXO7.Cell death discovery · 2026Article
- Integrated Network Pharmacology, Single-Cell Transcriptomics Unveil the Mechanistic Role of Morusin in Aortic Dissection.Journal of cellular and molecular medicine · 2026Article
- Veratramine influences the proliferation of human osteosarcoma cells through modulating the PI3K/AKT signaling cascade.Genes & diseases · 2026Article
141 more citing papers are in PubMed but not listed here.
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10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOsteosarcoma is the most common primary bone tumor in children and adolescents. Unfortunately, osteosarcoma treatments often fail due to the development of chemoresistance, of which the underlying molecular mechanisms still remain unclear. In this study, we demonstrated that HSP90AA1 gene is responsible for drug resistance in osteosarcoma through an autophagy-related mechanism.
methodsshRNAs were transfected into osteosarcoma cells for knockdown of HSP90AA1 gene. Stable HSP90AA1 overexpressing osteosarcoma cell lines were obtained by lentivirus infection. mRNA and protein expressions of HSP90AA1 in osteosarcoma cells were tested by quantitative real-time PCR and western blot, respectively. Autophagy of osteosarcoma cells was detected by western blot of LC3, transmission electron microscopy and fluorescence microscope. mRFP-GFP-LC3 lentiviral transfection was also performed to detect autophagic flux. NOD/SCID mices were inoculated with MG-63 tumor cells transfected with HSP90AA1 specific shRNA. TUNEL and LC3 staining were performed to detect apoptosis and autophagy of resected tumor tissues.
resultsDoxorubicin, cisplatin, and methotrexate, which are commonly used in chemotherapy, each induced HSP90AA1 upregulation in human osteosarcoma cells. Suppression of HSP90AA1 restored the sensitivity of osteosarcoma cells to chemotherapy both in vivo and in vitro. Mechanism study indicated that autophagy is responsible for the chemoresistance in osteosarcoma cells. HSP90AA1 increased drug resistance by inducing autophagy and inhibiting apoptosis. Suppression of HSP90AA1 diminished autophagic protection in response to chemotherapy in osteosarcoma cells. Moreover, HSP90AA1 promotes autophagy through PI3K/Akt/mTOR pathway and inhibits apoptosis through JNK/P38 pathway.
conclusionWe showed that chemotherapy agents can induce HSP90AA1 expression in osteosarcoma cells. And HSP90AA1, acting as an important regulator of autophagy, is a critical factor in the development of osteosarcoma chemoresistance both in vitro and in vivo. HSP90AA1 provides a novel therapeutic target for improving osteosarcoma treatment.
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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.