ArticleRadiation oncology (London, England)2015
Role of membrane Hsp70 in radiation sensitivity of tumor cells.
Article in Radiation oncology (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Lipid-gated vesicular trafficking directs HSPA1A to the plasma membrane through the endo-lysosomal network.Cell stress & chaperones · 2026Article
- Circulating Hsp70 Reflects Tumor Burden and Stage-Dependent Disease Progression Across Multiple Solid Tumor Entities.Cancers · 2026Article
- Radiomic analysis of the peritumoral zone identifies imaging signatures of glioma invasion associated with HSP70 expression.Frontiers in oncology · 2026Article
- Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.British journal of cancer · 2024Article
- The radiation- and chemo-sensitizing capacity of diclofenac can be predicted by a decreased lactate metabolism and stress response.Radiation oncology (London, England) · 2024Article
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
- Immunohistochemical, Flow Cytometric, and ELISA-Based Analyses of Intracellular, Membrane-Expressed, and Extracellular Hsp70 as Cancer Biomarkers.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Temozolomide increases heat shock proteins in extracellular vesicles released from glioblastoma cells.Molecular biology reports · 2022Article
- Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening.International journal of molecular sciences · 2022Review
- Combined Cytotoxic Effect of Inhibitors of Proteostasis on Human Colon Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Phosphatidylinositol Monophosphates Regulate the Membrane Localization of HSPA1A, a Stress-Inducible 70-kDa Heat Shock Protein.Biomolecules · 2022Article
- A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922.Frontiers in oncology · 2022Article
- Article
- Hsp70 in Liquid Biopsies-A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer.Cancers · 2021Article
- An aptamer interacting with heat shock protein 70 shows therapeutic effects and prognostic ability in serous ovarian cancer.Molecular therapy. Nucleic acids · 2021Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- Potential Role of Hsp70 and Activated NK Cells for Prediction of Prognosis in Glioblastoma Patients.Frontiers in molecular biosciences · 2021Article
- Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets.Cells · 2020Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in the cytosol and integrated in the plasma membrane of tumor cells via lipid anchorage. Following stress such as non-lethal irradiation Hsp70 synthesis is up-regulated. Intracellular located Hsp70 is known to exert cytoprotective properties, however, less is known about membrane (m)Hsp70. Herein, we investigate the role of mHsp70 in the sensitivity towards irradiation in tumor sublines that differ in their cytosolic and/or mHsp70 levels.
methodsThe isogenic human colon carcinoma sublines CX(+) with stable high and CX(-) with stable low expression of mHsp70 were generated by fluorescence activated cell sorting, the mouse mammary carcinoma sublines 4 T1 (4 T1 ctrl) and Hsp70 knock-down (4 T1 Hsp70 KD) were produced using the CRISPR/Cas9 system, and the Hsp70 down-regulation in human lung carcinoma sublines H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD was achieved by small interfering (si)RNA against Heat shock factor 1 (HSF-1). Cytosolic and mHsp70 was quantified by Western blot analysis/ELISA and flow cytometry; double strand breaks (DSBs) and apoptosis were measured by flow cytometry using antibodies against γH2AX and real-time PCR (RT-PCR) using primers and antibodies directed against apoptosis related genes; and radiation sensitivity was determined using clonogenic cell surviving assays.
resultsCX(+)/CX(-) tumor cells exhibited similar cytosolic but differed significantly in their mHsp70 levels, 4 T1 ctrl/4 T1 Hsp70 KD cells showed significant differences in their cytosolic and mHsp70 levels and H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD lung carcinoma cell sublines had similar mHsp70 but significantly different cytosolic Hsp70 levels. γH2AX was significantly up-regulated in irradiated CX(-) and 4 T1 Hsp70 KD with low basal mHsp70 levels, but not in their mHsp70 high expressing counterparts, irrespectively of their cytosolic Hsp70 content. After irradiation γH2AX, Caspase 3/7 and Annexin V were up-regulated in the lung carcinoma sublines, but no significant differences were observed in H1339 ctrl/H1339 HSF-1 KD, and EPLC-272H ctrl/EPLC-272H HSF-1 KD that exhibit identical mHsp70 but different cytosolic Hsp70 levels. Clonogenic cell survival was significantly lower in CX(-) and 4 T1 Hsp70 KD cells with low mHsp70 expression, than in CX+ and 4 T1 ctrl cells, whereas no difference in clonogenic cell survival was observed in H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/ EPLC-272H HSF-1 KD sublines with identical mHsp70 but different cytosolic Hsp70 levels.
conclusionIn summary, our results indicate that mHsp70 has an impact on radiation resistance.
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