دورية أكاديمية
Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.
| العنوان: | Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer. |
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| المؤلفون: | Li SY; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom., Hammarlund JA; School of Biomedical Engineering, Science and Health Systems, Bossone Research Center, Drexel University, Philadelphia, PA 19104., Wu G; Division of Human Genetics, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.; Division of Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229., Lian JW; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom., Howell SJ; Breast Biology Group, Manchester Breast Centre, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M20 4GJ, United Kingdom., Clarke RB; Breast Biology Group, Manchester Breast Centre, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M20 4GJ, United Kingdom., Adamson AD; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom., Gonçalves CF; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom., Hogenesch JB; Division of Human Genetics, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.; Division of Immunobiology, Center for Circadian Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229., Anafi RC; Department of Medicine, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Meng QJ; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Feb 13; Vol. 121 (7), pp. e2311854121. Date of Electronic Publication: 2024 Feb 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Breast Neoplasms*/pathology , Circadian Clocks*/genetics, Humans ; Female ; Circadian Rhythm ; Estrogens ; Prognosis |
| مستخلص: | Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis. Competing Interests: Competing interests statement:J.B.H. is on the scientific advisory board for Synchronicity Pharma. The other authors declare no competing interest. |
| التعليقات: | Comment in: Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2401496121. (PMID: 38422063) |
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| معلومات مُعتمدة: | R01 AG068577 United States AG NIA NIH HHS; R01 CA227485 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust |
| فهرسة مساهمة: | Keywords: breast cancer; circadian data ordering; circadian medicine; metastasis; prognosis |
| المشرفين على المادة: | 0 (Estrogens) |
| تواريخ الأحداث: | Date Created: 20240206 Date Completed: 20240208 Latest Revision: 20240229 |
| رمز التحديث: | 20240229 |
| مُعرف محوري في PubMed: | PMC10873596 |
| DOI: | 10.1073/pnas.2311854121 |
| PMID: | 38319971 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2311854121 |