دورية أكاديمية
Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner.
| العنوان: | Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner. |
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| المؤلفون: | Warde KM; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Smith LJ; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Liu L; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Stubben CJ; Bioinformatics Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Lohman BK; Bioinformatics Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Willett PW; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Ammer JL; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA., Castaneda-Hernandez G; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Imodoye SO; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Zhang C; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Jones KD; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Converso-Baran K; Frankel Cardiovascular Center Physiology and Phenotyping Core, University of Michigan, Ann Arbor, MI, USA., Ekiz HA; Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla Izmir, Turkey., Barry M; Department of Pathology, University of Utah, Salt Lake City, UT, USA., Clay MR; Department of Pathology, University of Colorado School of Medicine at Colorado Anschutz Medical Campus, Aurora, CO, USA., Kiseljak-Vassiliades K; Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine at Colorado Anschutz Medical Campus, Aurora, CO, USA., Giordano TJ; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.; Endocrine Oncology Program, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Hammer GD; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.; Endocrine Oncology Program, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Basham KJ; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. kaitlin.basham@hci.utah.edu. |
| المصدر: | Nature aging [Nat Aging] 2023 Jul; Vol. 3 (7), pp. 846-865. Date of Electronic Publication: 2023 May 25. |
| 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 US Country of Publication: United States NLM ID: 101773306 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-8465 (Electronic) Linking ISSN: 26628465 NLM ISO Abbreviation: Nat Aging Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Nature Publishing Group US, [2021]- |
| مواضيع طبية MeSH: | Adrenocortical Carcinoma*/genetics , Adrenal Cortex Neoplasms*/genetics, Male ; Animals ; Female ; Aging ; Cellular Senescence ; Signal Transduction ; Tumor Microenvironment |
| مستخلص: | Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted as tumors progress, which is recapitulated in patients in whom a low myeloid signature is associated with worse outcomes. Our study uncovers a role for myeloid cells in restraining adrenal cancer with substantial prognostic value and provides a model for interrogating pleiotropic effects of cellular senescence in cancer. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| التعليقات: | Comment in: Nat Aging. 2023 Jul;3(7):764-765. (PMID: 37291221) Comment in: Nat Rev Endocrinol. 2023 Aug;19(8):439. (PMID: 37328682) |
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| معلومات مُعتمدة: | K08 CA222620 United States CA NCI NIH HHS |
| تواريخ الأحداث: | Date Created: 20230525 Date Completed: 20230721 Latest Revision: 20231218 |
| رمز التحديث: | 20231218 |
| DOI: | 10.1038/s43587-023-00420-2 |
| PMID: | 37231196 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. | تدمد: | 2662-8465 |
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| DOI: | 10.1038/s43587-023-00420-2 |