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Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells
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Abstract
Changes in polysome-bound mRNA (translatome) are correlated closely with changes in the proteome in cells. Therefore, to better understand the processes mediating the response of glioblastoma to ionizing radiation (IR), we used polysome profiling to define the IR-induced translatomes of a set of human glioblastoma stem-like cell (GSC) lines. Although cell line specificity accounted for the largest proportion of genes within each translatome, there were also genes that were common to the GSC lines. In particular, analyses of the IR-induced common translatome identified components of the DNA damage response, consistent with a role for the translational control of gene expression in cellular radioresponse. Moreover, translatome analyses suggested that IR enhanced cap-dependent translation processes, an effect corroborated by the finding of increased eIF4F–cap complex formation detected after irradiation in all GSC lines. Translatome analyses also predicted that Golgi function was affected by IR. Accordingly, Golgi dispersal was detected after irradiation of each of the GSC lines. In addition to the common responses seen, translatome analyses predicted cell line–specific changes in mitochondria, as substantiated by changes in mitochondrial mass and DNA content. Together, these results suggest that analysis of radiation-induced translatomes can provide new molecular insights concerning the radiation response of cancer cells. More specifically, they suggest that the translational control of gene expression may provide a source of molecular targets for glioblastoma radiosensitization. Cancer Res; 76(10); 3078–87. ©2016 AACR.
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Global quantification of mammalian gene expression control
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“Under a variety of biological and experimental conditions (4-8), translational control has been shown to account for the discrepancies between the transcriptome and proteome.”
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Metadata
- Authors
- Wahba, A., Rath, B. H., Bisht, K., Camphausen, K., & Tofilon, P. J.
- Affiliations
- National Cancer Institute (US)
- Corresponding author
- Tofilon, Philip J.
- Venue
- Cancer Research
- Published
- 2016-05-12
- Volume
- 76
- Issue
- 10
- Pages
- 3078-3087
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4873349
- OpenAlex
- W2306982637
- Cited by
- 33
- References
- 3
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Division of Basic Sciences, Intramural Program, the National Cancer Institute (Z1ABC011372, Z1ABC011373)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- glioblastoma stem cells, ionizing radiation response, translatome, polysome profiling, translational regulation, DNA damage response, cap-dependent translation, eIF4F, mitochondrial mass, radiosensitization, cell line specificity
- MeSH terms
- Fluorescent Antibody Technique, Glioblastoma, Golgi Apparatus, Humans, Mitochondria, Polyribosomes, Radiation, Ionizing, RNA, Messenger, Protein Biosynthesis, Tumor Cells, Cultured, Neoplastic Stem Cells, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Real-Time Polymerase Chain Reaction
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