دورية أكاديمية
An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy.
| العنوان: | An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy. |
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| المؤلفون: | Liu PH; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Shah RB; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Li Y; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Arora A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ung PM; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Raman R; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Gorbatenko A; Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Kozono S; Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Zhou XZ; Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Brechin V; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan., Barbaro JM; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Albert Einstein College of Medicine, Bronx, NY, USA., Thompson R; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK., White RM; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Aguirre-Ghiso JA; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Heymach JV; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lu KP; Cancer Biology Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Silva JM; Department of Pathology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Panageas KS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Schlessinger A; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Maki RG; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Hofstra-Northwell School of Medicine and Cold Spring Harbor Laboratory, Hempstead, NY, USA., Skinner HD; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., de Stanchina E; Antitumor Assessment Core and Molecular Pharmacology Department, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sidi S; Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. samuel.sidi@mssm.edu.; Department of Cell, Developmental and Regenerative Biology, The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. samuel.sidi@mssm.edu. |
| المصدر: | Nature cell biology [Nat Cell Biol] 2019 Feb; Vol. 21 (2), pp. 203-213. Date of Electronic Publication: 2019 Jan 21. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Macmillan Magazines Ltd., [1999- |
| مواضيع طبية MeSH: | Signal Transduction*, Interleukin-1 Receptor-Associated Kinases/*metabolism , NIMA-Interacting Peptidylprolyl Isomerase/*metabolism , Neoplasms/*radiotherapy , Xenograft Model Antitumor Assays/*methods, Animals ; Cell Line, Tumor ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors ; Interleukin-1 Receptor-Associated Kinases/genetics ; MCF-7 Cells ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mutation ; NIMA-Interacting Peptidylprolyl Isomerase/antagonists & inhibitors ; NIMA-Interacting Peptidylprolyl Isomerase/genetics ; Neoplasms/genetics ; Neoplasms/metabolism ; Radiation Tolerance/drug effects ; Radiation Tolerance/genetics ; Tumor Suppressor Protein p53/genetics ; Zebrafish |
| مستخلص: | Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while tolerated in non-irradiated wild-type animals, we identified the benzimidazole anthelmintic oxfendazole. Surprisingly, oxfendazole acts via the inhibition of IRAK1, a kinase thus far implicated in interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) immune responses. IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88. Rather than stimulating nuclear factor-κB, radiation-activated IRAK1 prevented apoptosis mediated by the PIDDosome complex (comprising PIDD, RAIDD and caspase-2). Countering this pathway with IRAK1 inhibitors suppressed R-RT in tumour models derived from cancers in which TP53 mutations predict R-RT. Moreover, IRAK1 inhibitors synergized with inhibitors of PIN1, a prolyl isomerase essential for IRAK1 activation in response to pathogens and, as shown here, in response to ionizing radiation. These data identify an IRAK1 radiation-response pathway as a rational chemoradiation therapy target. |
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| معلومات مُعتمدة: | U54 OD020355 United States OD NIH HHS; F30 CA186448 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 CA168485 United States CA NCI NIH HHS; R01 GM135301 United States GM NIGMS NIH HHS; R01 CA178162 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (NIMA-Interacting Peptidylprolyl Isomerase) 0 (Tumor Suppressor Protein p53) EC 2.7.11.1 (IRAK1 protein, human) EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases) |
| تواريخ الأحداث: | Date Created: 20190122 Date Completed: 20190415 Latest Revision: 20210203 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC6428421 |
| DOI: | 10.1038/s41556-018-0260-7 |
| PMID: | 30664786 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1038/s41556-018-0260-7 |