dc.contributor.author | Therizols, G | en_US |
dc.contributor.author | Bash-Imam, Z | en_US |
dc.contributor.author | Panthu, B | en_US |
dc.contributor.author | Machon, C | en_US |
dc.contributor.author | Vincent, A | en_US |
dc.contributor.author | Ripoll, J | en_US |
dc.contributor.author | Nait-Slimane, S | en_US |
dc.contributor.author | Chalabi-Dchar, M | en_US |
dc.contributor.author | Gaucherot, A | en_US |
dc.contributor.author | Garcia, M | en_US |
dc.contributor.author | Laforêts, F | en_US |
dc.contributor.author | Marcel, V | en_US |
dc.contributor.author | Boubaker-Vitre, J | en_US |
dc.contributor.author | Monet, M-A | en_US |
dc.contributor.author | Bouclier, C | en_US |
dc.contributor.author | Vanbelle, C | en_US |
dc.contributor.author | Souahlia, G | en_US |
dc.contributor.author | Berthel, E | en_US |
dc.contributor.author | Albaret, MA | en_US |
dc.contributor.author | Mertani, HC | en_US |
dc.contributor.author | Prudhomme, M | en_US |
dc.contributor.author | Bertrand, M | en_US |
dc.contributor.author | David, A | en_US |
dc.contributor.author | Saurin, J-C | en_US |
dc.contributor.author | Bouvet, P | en_US |
dc.contributor.author | Rivals, E | en_US |
dc.contributor.author | Ohlmann, T | en_US |
dc.contributor.author | Guitton, J | en_US |
dc.contributor.author | Dalla Venezia, N | en_US |
dc.contributor.author | Pannequin, J | en_US |
dc.contributor.author | Catez, F | en_US |
dc.contributor.author | Diaz, J-J | en_US |
dc.date.accessioned | 2022-03-28T14:29:39Z | |
dc.date.available | 2021-12-10 | en_US |
dc.date.issued | 2022-01-10 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/77603 | |
dc.description.abstract | Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5'-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that "man-made" fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes. | en_US |
dc.format.extent | 173 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Antimetabolites, Antineoplastic | en_US |
dc.subject | Cell Line, Tumor | en_US |
dc.subject | Cell Survival | en_US |
dc.subject | Colorectal Neoplasms | en_US |
dc.subject | DNA Replication | en_US |
dc.subject | DNA, Neoplasm | en_US |
dc.subject | Drug Resistance, Neoplasm | en_US |
dc.subject | Drug Tolerance | en_US |
dc.subject | Fluorouracil | en_US |
dc.subject | HCT116 Cells | en_US |
dc.subject | Halogenation | en_US |
dc.subject | Humans | en_US |
dc.subject | Protein Biosynthesis | en_US |
dc.subject | RNA, Messenger | en_US |
dc.subject | RNA, Ribosomal | en_US |
dc.subject | Receptor, IGF Type 1 | en_US |
dc.subject | Ribosomes | en_US |
dc.subject | Xenograft Model Antitumor Assays | en_US |
dc.title | Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/s41467-021-27847-8 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35013311 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 13 | en_US |
dcterms.dateAccepted | 2021-12-10 | en_US |