دورية أكاديمية
Unchecked oxidative stress in skeletal muscle prevents outgrowth of disseminated tumour cells.
العنوان: | Unchecked oxidative stress in skeletal muscle prevents outgrowth of disseminated tumour cells. |
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المؤلفون: | Crist SB; Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, USA., Nemkov T; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Dumpit RF; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Dai J; Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Tapscott SJ; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Neurology, University of Washington, Seattle, WA, USA., True LD; Department of Urology, University of Washington, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Swarbrick A; The Kinghorn Cancer Centre and Cancer Research Theme, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia., Sullivan LB; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Nelson PS; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; Department of Urology, University of Washington, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Ghajar CM; Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cghajar@fredhutch.org.; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cghajar@fredhutch.org. |
المصدر: | Nature cell biology [Nat Cell Biol] 2022 Apr; Vol. 24 (4), pp. 538-553. Date of Electronic Publication: 2022 Apr 11. |
نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; 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: | Neoplasms*/metabolism , Oxidative Stress*/physiology, Animals ; Mice ; Muscle, Skeletal/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism |
مستخلص: | Skeletal muscle has long been recognized as an inhospitable site for disseminated tumour cells (DTCs). Yet its antimetastatic nature has eluded a thorough mechanistic examination. Here, we show that DTCs traffic to and persist within skeletal muscle in mice and in humans, which raises the question of how this tissue suppresses colonization. Results from mouse and organotypic culture models along with metabolomic profiling suggested that skeletal muscle imposes a sustained oxidative stress on DTCs that impairs their proliferation. Functional studies demonstrated that disrupting reduction-oxidation homeostasis via chemogenetic induction of reactive oxygen species slowed proliferation in a more fertile organ: the lung. Conversely, enhancement of the antioxidant potential of tumour cells through ectopic expression of catalase in the tumour or host mitochondria allowed robust colonization of skeletal muscle. These findings reveal a profound metabolic bottleneck imposed on DTCs and sustained by skeletal muscle. A thorough understanding of this biology could reveal previously undocumented DTC vulnerabilities that can be exploited to prevent metastasis in other more susceptible tissues. (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.) |
التعليقات: | Erratum in: Nat Cell Biol. 2022 Jul;24(7):1177. doi: 10.1038/s41556-022-00945-5. (PMID: 35610516) |
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معلومات مُعتمدة: | P30 CA015704 United States CA NCI NIH HHS; P50 CA097186 United States CA NCI NIH HHS; S10 OD021641 United States OD NIH HHS; R01 CA249528 United States CA NCI NIH HHS; T32 GM007270 United States GM NIGMS NIH HHS |
المشرفين على المادة: | 0 (Reactive Oxygen Species) |
تواريخ الأحداث: | Date Created: 20220412 Date Completed: 20220426 Latest Revision: 20240810 |
رمز التحديث: | 20240812 |
مُعرف محوري في PubMed: | PMC11312424 |
DOI: | 10.1038/s41556-022-00881-4 |
PMID: | 35411081 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4679 |
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DOI: | 10.1038/s41556-022-00881-4 |