Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner
| Autor: | Theodoros I. Roumeliotis, Jérôme Moreaux, Julia Gilhodes, Julien Mazieres, Marie-Jeanne Pillaire, Hélène Tourrière, Valérie Bergoglio, Julien N Bianco, Jean-Sébastien Hoffmann, Yea-Lih Lin, Amélie Lusque, Anne-Lyne Schmitz, Jyoti S. Choudhary, Magali Lacroix-Triki, Philippe Pasero |
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| Přispěvatelé: | Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claudius Regaud, CHU Toulouse [Toulouse], Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), The institute of cancer research [London], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Larose, Catherine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Timeless Science [SDV]Life Sciences [q-bio] General Physics and Astronomy Adenocarcinoma of Lung Breast Neoplasms Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins 02 engineering and technology [SDV.GEN] Life Sciences [q-bio]/Genetics Biology Genomic Instability Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Stress Physiological Cell Line Tumor medicine Humans Tumor growth lcsh:Science Adaptor Proteins Signal Transducing [SDV.GEN]Life Sciences [q-bio]/Genetics Multidisciplinary Replication stress Intracellular Signaling Peptides and Proteins Signal transducing adaptor protein General Chemistry HCT116 Cells 021001 nanoscience & nanotechnology medicine.disease Primary tumor 3. Good health Cell biology [SDV] Life Sciences [q-bio] 030104 developmental biology Cell culture Checkpoint Kinase 1 Cancer cell MCF-7 Cells lcsh:Q Cancer development biological phenomena cell phenomena and immunity Colorectal Neoplasms 0210 nano-technology DNA Damage HeLa Cells |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.910. ⟨10.1038/s41467-019-08886-8⟩ Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications, 2019, 10 (1), pp.910. ⟨10.1038/s41467-019-08886-8⟩ |
| ISSN: | 2041-1723 |
| Popis: | Oncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cancer cells adapt to RS, we have monitored the expression of different components of the ATR-CHK1 pathway in primary tumor samples. We show that unlike upstream components of the pathway, the checkpoint mediators Claspin and Timeless are overexpressed in a coordinated manner. Remarkably, reducing the levels of Claspin and Timeless in HCT116 cells to pretumoral levels impeded fork progression without affecting checkpoint signaling. These data indicate that high level of Claspin and Timeless increase RS tolerance by protecting replication forks in cancer cells. Moreover, we report that primary fibroblasts adapt to oncogene-induced RS by spontaneously overexpressing Claspin and Timeless, independently of ATR signaling. Altogether, these data indicate that enhanced levels of Claspin and Timeless represent a gain of function that protects cancer cells from of oncogene-induced RS in a checkpoint-independent manner. Oncogene-induced replication stress (RS) promotes cancer development. Here, the authors report that cancer cells adapt to oncogene-induced RS by overexpressing downstream components of ATR-CHK1 pathway, Claspin and Timeless, which have protective role at the replication forks independent of their checkpoint function. |
| Databáze: | OpenAIRE |
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