ArticlePloS one2014
Targeting GRP75 improves HSP90 inhibitor efficacy by enhancing p53-mediated apoptosis in hepatocellular carcinoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs.Nature biomedical engineering · 2026Article
- Mitochondria-Associated Endoplasmic Reticulum Membranes in Cancer: Hubs for Tumor Progression and Therapeutic Vulnerabilities.Cell biology international · 2026Review
- Growth hormone - releasing hormone in the immune system.Reviews in endocrine & metabolic disorders · 2025Review
- The Role of HSP90 and TRAP1 Targets on Treatment in Hepatocellular Carcinoma.Molecular biotechnology · 2025Review
- Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS.Acta neuropathologica communications · 2025Article
- Cardioprotective effect of Yiqi Huoxue decoction on post-myocardial infarction injury mediated by CaFrontiers in cardiovascular medicine · 2025Article
- Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.International journal of molecular sciences · 2023Article
- A Regulatory Loop Involving miR-200c and NF-κB Modulates Mortalin Expression and Increases Cisplatin Sensitivity in an Ovarian Cancer Cell Line Model.International journal of molecular sciences · 2022Article
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy.Frontiers in cardiovascular medicine · 2021Review
- Autophagy-A Hidden but Important Actor on Oral Cancer Scene.International journal of molecular sciences · 2020Review
- Differential Expression of HSP90Journal of pharmacopuncture · 2019Article
- Cooperation between Hsp90 and mortalin/GRP75 in resistance to cell death induced by complement C5b-9.Cell death & disease · 2018Article
- One protein, different cell fate: the differential outcome of depleting GRP75 during oxidative stress in neurons.Cell death & disease · 2018Article
- Glucose-regulated protein 75 determines ER-mitochondrial coupling and sensitivity to oxidative stress in neuronal cells.Cell death discovery · 2017Article
- The human HSP70 family of chaperones: where do we stand?Cell stress & chaperones · 2016Review
- Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.Cell stress & chaperones · 2016Article
- The Role of the Membrane-Initiated Heat Shock Response in Cancer.Frontiers in molecular biosciences · 2016Review
- A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2.Oncotarget · 2015Article
- A phase I and pharmacokinetic study of ganetespib (STA-9090) in advanced hepatocellular carcinoma.Investigational new drugs · 2015Article
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
Heat shock protein 90 (HSP90) inhibitors are potential drugs for cancer therapy. The inhibition of HSP90 on cancer cell growth largely through degrading client proteins, like Akt and p53, therefore, triggering cancer cell apoptosis. Here, we show that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70) family, which, in turn, attenuates the anti-growth effect of HSP90 inhibition on cancer cells. Additionally, 17-AAG enhanced binding of GRP75 and p53, resulting in the retention of p53 in the cytoplasm. Blocking GRP75 with its inhibitor MKT-077 potentiated the anti-tumor effects of 17-AAG by disrupting the formation of GRP75-p53 complexes, thereby facilitating translocation of p53 into the nuclei and leading to the induction of apoptosis-related genes. Finally, dual inhibition of HSP90 and GRP75 was found to significantly inhibit tumor growth in a liver cancer xenograft model. In conclusion, the GRP75 inhibitor MKT-077 enhances 17-AAG-induced apoptosis in HCCs and increases p53-mediated inhibition of tumor growth in vivo. Dual targeting of GRP75 and HSP90 may be a useful strategy for the treatment of HCCs.
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