Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells
| Autor: | Kheem S. Bisht, Philip J. Tofilon, Kevin Camphausen, Barbara H. Rath, Amy Wahba |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research DNA damage Cell Fluorescent Antibody Technique Golgi Apparatus Biology Real-Time Polymerase Chain Reaction Article 03 medical and health sciences Radiation Ionizing Gene expression Tumor Cells Cultured medicine Humans RNA Messenger Gene Oligonucleotide Array Sequence Analysis Genetics Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Translation (biology) Mitochondria Cell biology Gene expression profiling 030104 developmental biology medicine.anatomical_structure Oncology Polyribosomes Protein Biosynthesis Proteome Cancer cell Neoplastic Stem Cells Glioblastoma |
| Zdroj: | Cancer Research. 76:3078-3087 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-15-3050 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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