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Your search keyword '"Team 'RNA splicing, cell signaling and response to therapies'"' showing total 2 results
Start Over Author "Team 'RNA splicing, cell signaling and response to therapies'" Publisher elsevier bv
2 results on '"Team 'RNA splicing, cell signaling and response to therapies'"'

1. ARF promotes the degradation of the Epidermal Growth Factor Receptor by the lysosome

Author

P. Perron, Anais Beaumont, Sylvie Gazzeri, Celine Barrial, Beatrice Eymin, Anne-Sophie Hatat, Delphine Dayde, Eymin, Beatrice, Team 'RNA splicing, cell signaling and response to therapies', Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
0301 basic medicine, Reading Frames, Lung Neoplasms, EGFR, [SDV]Life Sciences [q-bio], Mutant, Down-Regulation, Apoptosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Degradation, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Lysosome, medicine, Humans, Epidermal growth factor receptor, Phosphorylation, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Epidermal Growth Factor, biology, Oncogene, ADP-Ribosylation Factors, Wild type, ARF, Cell Biology, ErbB Receptors, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Cell culture, 030220 oncology & carcinogenesis, Mutation, Cancer research, biology.protein, Lung cancer, Lysosomes, Signal Transduction
Abstract

International audience; Epidermal Growth Factor Receptor (EGFR) signaling regulates multiple cellular processes including proliferation , survival and apoptosis, and is attenuated by lysosomal receptor degradation. EGFR is a potent oncogene and activating mutations of EGFR are critical determinants of oncogenic transformation as well as therapeutic targets in non-small cell lung cancer. We previously demonstrated that wild type and mutant EGFRs repress the expression of the ARF tumor suppressor to promote the survival of lung tumor cells. In this study, using transient transfection systems in CHO EGFR-null cells as well as in various lung tumor cell lines carrying wild type or activated mutant EGFR, we show that ARF downregulates the expression of EGFR protein by reducing its half life. In wild type EGFR cells, ARF promotes canonical lysosomal degradation of the receptor through enhanced phosphorylation of EGFR-Y1045 and Cbl-Y731. In contrast, in mutant EGFR cells, ARF induces EGFR degradation by activating a non-canonical AKT-dependent lysosomal pathway. Taken together, these results uncover a feedback loop by which ARF may control EGFR turnover to restrain oncogenic signaling. They also highlight distinct degradation promoting pathways between wild type and mutant EGFRs in response to ARF.

Published
2018
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2. Nuclear translocation of IGF1R by intracellular amphiregulin contributes to the resistance of lung tumour cells to EGFR-TKI

Author

Laetitia Vanwonterghem, Jean-Luc Coll, Beatrice Eymin, Marie Guerard, Laurence David-Boudet, Sylvie Gazzeri, P. Perron, Anne-Sophie Hatat, Amandine Hurbin, Thomas Robin, Benoit Busser, Sylvie Lantuejoul, Team 'RNA splicing, cell signaling and response to therapies', Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Team 'Cancer targets and experimental therapeutics', Centre Hospitalier Universitaire [Grenoble] (CHU), Eymin, Beatrice, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
0301 basic medicine, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], Apoptosis, MESH: EGFR-TKI, IGF1R, Lung cancer, Nuclear trafficking, Resistance, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Amphiregulin, Receptor tyrosine kinase, Receptor, IGF Type 1, 03 medical and health sciences, Gefitinib, Epidermal growth factor, Cell Line, Tumor, medicine, Humans, skin and connective tissue diseases, Protein Kinase Inhibitors, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Insulin-like growth factor 1 receptor, Cell Nucleus, biology, Chemistry, Receptors, Somatomedin, Cell Cycle Checkpoints, medicine.disease, Adenocarcinoma, Mucinous, Xenograft Model Antitumor Assays, respiratory tract diseases, 3. Good health, [SDV] Life Sciences [q-bio], body regions, Protein Transport, Cell nucleus, 030104 developmental biology, medicine.anatomical_structure, Oncology, A549 Cells, Drug Resistance, Neoplasm, Cancer research, biology.protein, Signal transduction, Signal Transduction, medicine.drug
Abstract

International audience; Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xeno-grafts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin. Amphiregulin allows the binding of IGF1R to importin-b1 and promotes its nuclear transport. The nuclear accumulation of IGF1R by amphiregulin induces cell cycle arrest through p21 WAF1/CIP1 upregulation, and prevents the induction of apoptosis in response to gefitinib. These results identify amphiregulin as the first nuclear localization signal-containing protein that interacts with IGF1R and allows its nuclear translocation. Furthermore they indicate that nuclear expression of IGF1R contributes to EGFR-TKI resistance in lung cancer.

Published
2018
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