دورية أكاديمية
Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.
العنوان: | Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. |
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المؤلفون: | McDonald OG; Department of Pathology, Microbiology and Immunology, Vanderbilt-Ingram Cancer Center, and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Li X; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Saunders T; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Tryggvadottir R; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Mentch SJ; Duke Cancer Institute, Duke Molecular Physiology Institute, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA., Warmoes MO; Duke Cancer Institute, Duke Molecular Physiology Institute, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA., Word AE; Department of Pathology, Microbiology and Immunology, Vanderbilt-Ingram Cancer Center, and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Carrer A; Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Salz TH; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Natsume S; Department of Pathology, Microbiology and Immunology, Vanderbilt-Ingram Cancer Center, and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Stauffer KM; Department of Pathology, Microbiology and Immunology, Vanderbilt-Ingram Cancer Center, and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Makohon-Moore A; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Zhong Y; Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Wu H; Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, USA., Wellen KE; Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Locasale JW; Duke Cancer Institute, Duke Molecular Physiology Institute, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA., Iacobuzio-Donahue CA; Departments of Pathology and Human Oncology and Pathogenesis Program, David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Feinberg AP; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Departments of Medicine, Biomedical Engineering and Mental Health, Johns Hopkins University Schools of Medicine, Engineering and Public Health, Baltimore, Maryland, USA. |
المصدر: | Nature genetics [Nat Genet] 2017 Mar; Vol. 49 (3), pp. 367-376. Date of Electronic Publication: 2017 Jan 16. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
مواضيع طبية MeSH: | Epigenesis, Genetic/*genetics , Glucose/*metabolism , Neoplasm Metastasis/*genetics , Pancreatic Neoplasms/*genetics, Carcinogenesis/genetics ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/metabolism ; Chromatin/genetics ; Epigenomics/methods ; Gene Expression/genetics ; Heterochromatin/genetics ; Histones/genetics ; Humans ; Pancreatic Neoplasms/metabolism |
مستخلص: | During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis. |
التعليقات: | Comment in: Nat Rev Cancer. 2017 Feb 23;17 (3):141. (PMID: 28228644) Comment in: Cancer Cell. 2017 Mar 13;31(3):309-310. (PMID: 28292434) |
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معلومات مُعتمدة: | F31 CA180682 United States CA NCI NIH HHS; R01 CA179991 United States CA NCI NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; R00 CA168997 United States CA NCI NIH HHS; R01 CA054358 United States CA NCI NIH HHS; P50 CA095103 United States CA NCI NIH HHS; R01 CA140599 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Chromatin) 0 (Heterochromatin) 0 (Histones) IY9XDZ35W2 (Glucose) |
تواريخ الأحداث: | Date Created: 20170117 Date Completed: 20170905 Latest Revision: 20220331 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5695682 |
DOI: | 10.1038/ng.3753 |
PMID: | 28092686 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1546-1718 |
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DOI: | 10.1038/ng.3753 |