The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer
The Integrated Stress Response (ISR) is a cytoprotective pathway upregulated in many cancers. Here the authors show that the activation of PERK/p-eIF2α arm of ISR enhances ERK phosphorylation through translation repression of DUSP6, thus resulting in KRAS-driven lung tumorigenesis.
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-021-24661-0 |
| _version_ | 1818346299161837568 |
|---|---|
| author | Nour Ghaddar Shuo Wang Bethany Woodvine Jothilatha Krishnamoorthy Vincent van Hoef Cedric Darini Urszula Kazimierczak Nicolas Ah-son Helmuth Popper Myriam Johnson Leah Officer Ana Teodósio Massimo Broggini Koren K. Mann Maria Hatzoglou Ivan Topisirovic Ola Larsson John Le Quesne Antonis E. Koromilas |
| author_facet | Nour Ghaddar Shuo Wang Bethany Woodvine Jothilatha Krishnamoorthy Vincent van Hoef Cedric Darini Urszula Kazimierczak Nicolas Ah-son Helmuth Popper Myriam Johnson Leah Officer Ana Teodósio Massimo Broggini Koren K. Mann Maria Hatzoglou Ivan Topisirovic Ola Larsson John Le Quesne Antonis E. Koromilas |
| author_sort | Nour Ghaddar |
| collection | DOAJ |
| description | The Integrated Stress Response (ISR) is a cytoprotective pathway upregulated in many cancers. Here the authors show that the activation of PERK/p-eIF2α arm of ISR enhances ERK phosphorylation through translation repression of DUSP6, thus resulting in KRAS-driven lung tumorigenesis. |
| first_indexed | 2024-12-13T17:16:03Z |
| format | Article |
| id | doaj.art-c5184c726c2a4e1fa460c06a009a5df9 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-13T17:16:03Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c5184c726c2a4e1fa460c06a009a5df92022-12-21T23:37:25ZengNature PortfolioNature Communications2041-17232021-07-0112111510.1038/s41467-021-24661-0The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancerNour Ghaddar0Shuo Wang1Bethany Woodvine2Jothilatha Krishnamoorthy3Vincent van Hoef4Cedric Darini5Urszula Kazimierczak6Nicolas Ah-son7Helmuth Popper8Myriam Johnson9Leah Officer10Ana Teodósio11Massimo Broggini12Koren K. Mann13Maria Hatzoglou14Ivan Topisirovic15Ola Larsson16John Le Quesne17Antonis E. Koromilas18Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalLeicester Cancer Research Centre, University of LeicesterLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalDepartment of Oncology-Pathology, Science for Life Laboratory, Karolinska InstituteLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalDiagnostic and Research Institute of Pathology, Medical University of GrazLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalMRC Toxicology Unit, University of CambridgeMRC Toxicology Unit, University of CambridgeLaboratory of Molecular Pharmacology IRCCS—Istituto di Ricerche Farmacologiche “Mario Negri”Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalDepartment of Genetics, Case Western Reserve UniversityLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalDepartment of Oncology-Pathology, Science for Life Laboratory, Karolinska InstituteLeicester Cancer Research Centre, University of LeicesterLady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General HospitalThe Integrated Stress Response (ISR) is a cytoprotective pathway upregulated in many cancers. Here the authors show that the activation of PERK/p-eIF2α arm of ISR enhances ERK phosphorylation through translation repression of DUSP6, thus resulting in KRAS-driven lung tumorigenesis.https://doi.org/10.1038/s41467-021-24661-0 |
| spellingShingle | Nour Ghaddar Shuo Wang Bethany Woodvine Jothilatha Krishnamoorthy Vincent van Hoef Cedric Darini Urszula Kazimierczak Nicolas Ah-son Helmuth Popper Myriam Johnson Leah Officer Ana Teodósio Massimo Broggini Koren K. Mann Maria Hatzoglou Ivan Topisirovic Ola Larsson John Le Quesne Antonis E. Koromilas The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer Nature Communications |
| title | The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer |
| title_full | The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer |
| title_fullStr | The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer |
| title_full_unstemmed | The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer |
| title_short | The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer |
| title_sort | integrated stress response is tumorigenic and constitutes a therapeutic liability in kras driven lung cancer |
| url | https://doi.org/10.1038/s41467-021-24661-0 |
| work_keys_str_mv | AT nourghaddar theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT shuowang theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT bethanywoodvine theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT jothilathakrishnamoorthy theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT vincentvanhoef theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT cedricdarini theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT urszulakazimierczak theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT nicolasahson theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT helmuthpopper theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT myriamjohnson theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT leahofficer theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT anateodosio theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT massimobroggini theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT korenkmann theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT mariahatzoglou theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT ivantopisirovic theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT olalarsson theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT johnlequesne theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT antonisekoromilas theintegratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT nourghaddar integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT shuowang integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT bethanywoodvine integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT jothilathakrishnamoorthy integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT vincentvanhoef integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT cedricdarini integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT urszulakazimierczak integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT nicolasahson integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT helmuthpopper integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT myriamjohnson integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT leahofficer integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT anateodosio integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT massimobroggini integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT korenkmann integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT mariahatzoglou integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT ivantopisirovic integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT olalarsson integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT johnlequesne integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer AT antonisekoromilas integratedstressresponseistumorigenicandconstitutesatherapeuticliabilityinkrasdrivenlungcancer |