دورية أكاديمية
Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis.
العنوان: | Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. |
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المؤلفون: | Frankowski KJ; Specialized Chemistry Center, The University of Kansas, Lawrence, KS 66047, USA., Wang C; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Patnaik S; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Schoenen FJ; Specialized Chemistry Center, The University of Kansas, Lawrence, KS 66047, USA., Southall N; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Li D; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Teper Y; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Sun W; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Kandela I; Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA., Hu D; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Dextras C; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Knotts Z; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Bian Y; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Norton J; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Titus S; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Lewandowska MA; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Wen Y; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Farley KI; Departments of Molecular Biophysics and Biochemistry, Genetics, and Therapeutic Radiology, Yale University and Yale School of Medicine, New Haven, CT 06520, USA., Griner LM; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Sultan J; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Meng Z; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA., Zhou M; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA., Vilimas T; Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Fort Detrick, Frederick, MD 21702, USA., Powers AS; Laboratory of Pathology, Center for Cancer Research, NIH, Bethesda, MD 20892, USA., Kozlov S; Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Fort Detrick, Frederick, MD 21702, USA., Nagashima K; Electron Microscope Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Quadri HS; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA., Fang M; Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA., Long C; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Khanolkar O; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Chen W; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Kang J; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Huang H; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Chow E; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Goldberg E; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Feldman C; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Xi R; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA., Kim HR; Department of Human Genetics, Cancer Biology Graduate Program, Emory University School of Medicine, Atlanta, GA 30322, USA., Sahagian G; Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA., Baserga SJ; Departments of Molecular Biophysics and Biochemistry, Genetics, and Therapeutic Radiology, Yale University and Yale School of Medicine, New Haven, CT 06520, USA., Mazar A; Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA., Ferrer M; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Zheng W; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA., Shilatifard A; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Aubé J; Specialized Chemistry Center, The University of Kansas, Lawrence, KS 66047, USA., Rudloff U; Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. s-huang2@northwestern.edu maruganj@mail.nih.gov rudloffu@mail.nih.gov., Marugan JJ; NIH (National Institutes of Health) Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA. s-huang2@northwestern.edu maruganj@mail.nih.gov rudloffu@mail.nih.gov., Huang S; Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA. s-huang2@northwestern.edu maruganj@mail.nih.gov rudloffu@mail.nih.gov. |
المصدر: | Science translational medicine [Sci Transl Med] 2018 May 16; Vol. 10 (441). |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
مواضيع طبية MeSH: | Cell Nucleolus/*pathology , Neoplasm Metastasis/*drug therapy , Pyrimidines/*therapeutic use , Pyrroles/*therapeutic use, Animals ; Cell Line, Tumor ; Cell Nucleolus/drug effects ; Cell Nucleolus/metabolism ; Cell Nucleolus/ultrastructure ; Cell Proliferation/drug effects ; Chromatin/metabolism ; DNA, Ribosomal/genetics ; Humans ; Male ; Mice ; Neoplasm Invasiveness ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Peptide Elongation Factor 1/metabolism ; Promoter Regions, Genetic/genetics ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Pyrroles/chemistry ; Pyrroles/pharmacology ; RNA Polymerase I/metabolism ; RNA Precursors/biosynthesis ; Survival Analysis ; Transcription, Genetic/drug effects ; Xenograft Model Antitumor Assays |
مستخلص: | Metastasis remains a leading cause of cancer mortality due to the lack of specific inhibitors against this complex process. To identify compounds selectively targeting the metastatic state, we used the perinucleolar compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds. Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2. Thus, metarrestin represents a potential therapeutic approach for the treatment of metastatic cancer. (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
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معلومات مُعتمدة: | T32 GM007223 United States GM NIGMS NIH HHS; U54 HG005031 United States HG NHGRI NIH HHS; F31 DE026946 United States DE NIDCR NIH HHS; R01 GM115710 United States GM NIGMS NIH HHS; P30 CA060553 United States CA NCI NIH HHS; R01 GM078555 United States GM NIGMS NIH HHS |
المشرفين على المادة: | 0 (Chromatin) 0 (DNA, Ribosomal) 0 (EEF1A2 protein, human) 0 (Peptide Elongation Factor 1) 0 (Pyrimidines) 0 (Pyrroles) 0 (RNA Precursors) 0 (metarrestin) EC 2.7.7.6 (RNA Polymerase I) |
تواريخ الأحداث: | Date Created: 20180518 Date Completed: 20190920 Latest Revision: 20240620 |
رمز التحديث: | 20240620 |
مُعرف محوري في PubMed: | PMC6176865 |
DOI: | 10.1126/scitranslmed.aap8307 |
PMID: | 29769289 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1946-6242 |
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DOI: | 10.1126/scitranslmed.aap8307 |