دورية أكاديمية
Cycling cancer persister cells arise from lineages with distinct programs.
| العنوان: | Cycling cancer persister cells arise from lineages with distinct programs. |
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| المؤلفون: | Oren Y; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Tsabar M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA., Cuoco MS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Amir-Zilberstein L; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Cabanos HF; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Departments of Medicine, Harvard Medical School, Boston, MA, USA., Hütter JC; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Hu B; Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Thakore PI; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Genentech, South San Francisco, CA, USA., Tabaka M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Fulco CP; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Bristol Myers Squibb, Cambridge, MA, USA., Colgan W; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Cuevas BM; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Hurvitz SA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.; Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA., Slamon DJ; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.; Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA., Deik A; Metabolomics Platform, Broad Institute, Cambridge, MA, USA., Pierce KA; Metabolomics Platform, Broad Institute, Cambridge, MA, USA., Clish C; Metabolomics Platform, Broad Institute, Cambridge, MA, USA., Hata AN; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Departments of Medicine, Harvard Medical School, Boston, MA, USA., Zaganjor E; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Lahav G; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Politi K; Section of Medical Oncology, Department of Pathology, Yale School of Medicine, New Haven, CT, USA.; Yale Cancer Center, New Haven, CT, USA., Brugge JS; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. joan_brugge@hms.harvard.edu.; Ludwig Center at Harvard, Boston, MA, USA. joan_brugge@hms.harvard.edu., Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. aviv.regev.sc@gmail.com.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. aviv.regev.sc@gmail.com.; Howard Hughes Medical Institute, Chevy Chase, MD, USA. aviv.regev.sc@gmail.com.; Genentech, South San Francisco, CA, USA. aviv.regev.sc@gmail.com. |
| المصدر: | Nature [Nature] 2021 Aug; Vol. 596 (7873), pp. 576-582. Date of Electronic Publication: 2021 Aug 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| مواضيع طبية MeSH: | Cell Cycle*/drug effects , Cell Lineage*/drug effects, Neoplasm Recurrence, Local/*drug therapy , Neoplasm Recurrence, Local/*pathology , Neoplasms/*drug therapy , Neoplasms/*pathology, Antioxidants/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Clone Cells/drug effects ; Clone Cells/metabolism ; Clone Cells/pathology ; DNA Barcoding, Taxonomic ; Fatty Acids/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lentivirus/genetics ; Neoplasm Recurrence, Local/genetics ; Neoplasms/genetics ; Neoplasms/metabolism ; Oncogene Proteins/antagonists & inhibitors ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Transcription, Genetic/drug effects |
| مستخلص: | Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure 1 , where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment 2 . Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence. (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.) |
| التعليقات: | Comment in: Nature. 2021 Aug;596(7873):491-493. (PMID: 34381221) Comment in: Nat Rev Cancer. 2021 Nov;21(11):683. (PMID: 34522021) Comment in: Signal Transduct Target Ther. 2021 Dec 24;6(1):437. (PMID: 34952897) Comment in: Nat Rev Cancer. 2022 Aug;22(8):434-435. (PMID: 35538369) |
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| معلومات مُعتمدة: | United States HHMI Howard Hughes Medical Institute; R01 CA148761 United States CA NCI NIH HHS; F32 AI138458 United States AI NIAID NIH HHS; P30 CA016042 United States CA NCI NIH HHS; R01 CA121210 United States CA NCI NIH HHS; R01 CA120247 United States CA NCI NIH HHS; R01 CA120247 United States CA NCI NIH HHS; P30 CA016359 United States CA NCI NIH HHS; K08 CA197389 United States CA NCI NIH HHS; P50 CA196530 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Antioxidants) 0 (Fatty Acids) 0 (Oncogene Proteins) 0 (Reactive Oxygen Species) |
| تواريخ الأحداث: | Date Created: 20210812 Date Completed: 20220211 Latest Revision: 20230215 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9209846 |
| DOI: | 10.1038/s41586-021-03796-6 |
| PMID: | 34381210 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-4687 |
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| DOI: | 10.1038/s41586-021-03796-6 |