ArticleInternational journal of molecular sciences2021
Disruption of the Complex between GAPDH and Hsp70 Sensitizes C6 Glioblastoma Cells to Hypoxic Stress.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies.International journal of molecular sciences · 2025Review
- Selection of reference genes and proteins for expression studies in pediatric gliomas.Discover oncology · 2025Article
- Redox-Regulated Pathways in Glioblastoma Stem-like Cells: Mechanistic Insights and Therapeutic Implications.Brain sciences · 2025Review
- Plant defense-directed discovery of a natural anti-psoriasis agent targeting GAPDH.Science advances · 2025Article
- Small molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in estrogen receptor-positive breast cancer overcomes tamoxifen resistance.Breast cancer research : BCR · 2024Article
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- Suppressive Effect of Chemically Induced Hypoxia on Glioblastoma Cell Proliferation.Bulletin of experimental biology and medicine · 2023Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Molecular signature to predict quality of life and survival with glioblastoma using Multiview omics model.PloS one · 2023Article
- 2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins.Antioxidants (Basel, Switzerland) · 2022Article
- 3-Bromo-Isoxazoline Derivatives Inhibit GAPDH Enzyme in PDAC Cells Triggering Autophagy and Apoptotic Cell Death.Cancers · 2022Article
- Acute Hypoxia Alters Extracellular Vesicle Signatures and the Brain Citrullinome of Naked Mole-Rats (International journal of molecular sciences · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia, which commonly accompanies tumor growth, depending on its strength may cause the enhancement of tumorigenicity of cancer cells or their death. One of the proteins targeted by hypoxia is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and we demonstrated here that hypoxia mimicked by treating C6 rat glioblastoma cells with cobalt chloride caused an up-regulation of the enzyme expression, while further elevation of hypoxic stress caused the enzyme aggregation concomitantly with cell death. Reduction or elevation of GAPDH performed with the aid of specific shRNAs resulted in the augmentation of the tumorigenicity of C6 cells or their sensitization to hypoxic stress. Another hypoxia-regulated protein, Hsp70 chaperone, was shown to prevent the aggregation of oxidized GAPDH and to reduce hypoxia-mediated cell death. In order to release the enzyme molecules from the chaperone, we employed its inhibitor, derivative of colchicine. The compound was found to substantially increase aggregation of GAPDH and to sensitize C6 cells to hypoxia both in vitro and in animals bearing tumors with distinct levels of the enzyme expression. In conclusion, blocking the chaperonic activity of Hsp70 and its interaction with GAPDH may become a promising strategy to overcome tumor resistance to multiple environmental stresses and enhance existing therapeutic tools.
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