ArticleOncotarget2016
Knock-down of Hdj2/DNAJA1 co-chaperone results in an unexpected burst of tumorigenicity of C6 glioblastoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- DNAJA: emerging targets for anti-tumor therapy.Future oncology (London, England) · 2025Review
- Leveraging the Structure of DNAJA1 to Discover Novel Potential Pancreatic Cancer Therapies.Biomolecules · 2022Article
- Hsp40s play distinct roles during the initial stages of apolipoprotein B biogenesis.Molecular biology of the cell · 2022Article
- The Role of Heat Shock Protein 40 in Carcinogenesis and Biology of Colorectal Cancer.Current pharmaceutical design · 2022Review
- Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.International journal of molecular sciences · 2021Review
- DNAJA1 Dysregulates Metabolism Promoting an Antiapoptotic Phenotype in Pancreatic Ductal Adenocarcinoma.Journal of proteome research · 2021Article
- Ferroptosis-related gene signature as a prognostic marker for lower-grade gliomas.Journal of cellular and molecular medicine · 2021Article
- Molecular subtyping of glioblastoma based on immune-related genes for prognosis.Scientific reports · 2020Article
- Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance.Scientific reports · 2020Article
- KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis.Oncogene · 2020Article
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- The molecular chaperone Hsp70 from the thermotolerant Diptera species differs from the Drosophila paralog in its thermostability and higher refolding capacity at extreme temperatures.Cell stress & chaperones · 2019Article
- Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells.Oncotarget · 2018Article
- Sensitizing tumor cells to conventional drugs: HSP70 chaperone inhibitors, their selection and application in cancer models.Cell death & disease · 2018Article
- Induction of Chaperone Synthesis in Human Neuronal Cells Blocks Oxidative Stress-Induced Aging.Acta naturaeArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chaperone system based on Hsp70 and proteins of the DnaJ family is known to protect tumor cells from a variety of cytotoxic factors, including anti-tumor therapy. To analyze whether this also functions in a highly malignant brain tumor, we knocked down the expression of Hsp70 (HSPA1A) and its two most abundant co-chaperones, Hdj1 (DNAJB1) and Hdj2 (DNAJA1) in a C6 rat glioblastoma cell line. As expected, tumor depletion of Hsp70 caused a substantial reduction in its growth rate and increased the survival of tumor-bearing animals, whereas the reduction of Hdj1 expression had no effect. Unexpectedly, a reduction in the expression of Hdj2 led to the enhanced aggressiveness of the C6 tumor, demonstrated by its rapid growth, metastasis formation and a 1.5-fold reduction in the lifespan of tumor-bearing animals. The in vitro reduction of Hdj2 expression reduced spheroid density and simultaneously enhanced the migration and invasion of C6 cells. At the molecular level, a knock-down of Hdj2 led to the relocation of N-cadherin and the enhanced activity of metalloproteinases 1, 2, 8 and 9, which are markers of highly malignant cancer cells. The changes in the actin cytoskeleton in Hdj2-depleted cells indicate that the protein is also important for prevention of the amoeboid-like transition of tumor cells. The results of this study uncover a completely new role for the Hdj2 co-chaperone in tumorigenicity and suggest that the protein is a potential drug target.
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