title: Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells.
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.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Amy
authors.initials: A
authors.lastname: Wahba
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Rath
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kheem
authors.initials: K
authors.lastname: Bisht
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland. tofionp@mail.nih.gov.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Tofilon
mesh_terms: D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D014176:Protein Biosynthesis / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger