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.) |
| References: | Genes Dev. 2015 Apr 1;29(7):772-83. (PMID: 25838545) J Cell Biol. 1997 Jun 2;137(5):965-74. (PMID: 9166399) Clin Cancer Res. 2012 Nov 15;18(22):6339-47. (PMID: 22991414) Mol Biol Cell. 2007 Jun;18(6):2296-304. (PMID: 17429075) Mol Cancer Ther. 2014 Nov;13(11):2537-46. (PMID: 25277384) J Ultrastruct Res. 1964 Apr;10:224-43. (PMID: 14166291) Cell Cycle. 2006 Apr;5(7):735-9. (PMID: 16582637) Mol Biol Cell. 2003 Jun;14(6):2425-35. (PMID: 12808040) Science. 2013 Jul 5;341(6141):84-7. (PMID: 23828940) J Proteomics. 2009 Nov 2;73(1):112-22. (PMID: 19709643) J Biomol Screen. 2009 Oct;14(9):1045-53. (PMID: 19762548) J Biol Chem. 2009 Feb 13;284(7):4090-101. (PMID: 19015260) Nucleic Acids Res. 1998 Sep 1;26(17):3871-6. (PMID: 9705492) FASEB J. 2010 Nov;24(11):4575-84. (PMID: 20643906) Curr Opin Cell Biol. 2006 Jun;18(3):325-34. (PMID: 16687244) Nature. 2015 Sep 10;525(7568):261-4. (PMID: 26308893) Cancer. 2008 Aug 15;113(4):861-9. (PMID: 18543322) RNA. 2011 Aug;17(8):1578-88. (PMID: 21693620) Anal Chem. 1996 Mar 1;68(5):850-8. (PMID: 8779443) Int J Oncol. 2007 Oct;31(4):741-51. (PMID: 17786304) J Cell Biol. 1998 Oct 5;143(1):35-47. (PMID: 9763419) Br J Cancer. 2007 May 21;96(10):1613-20. (PMID: 17437010) Histochem Cell Biol. 2008 Jan;129(1):13-31. (PMID: 18046571) Cancer Lett. 2013 Jan 28;328(2):207-11. (PMID: 23059758) Exp Cell Res. 1980 Jun;127(2):285-91. (PMID: 6155282) J Cell Biochem. 2009 May 15;107(2):189-93. (PMID: 19288520) J Biol Chem. 2010 Jul 9;285(28):21209-13. (PMID: 20444696) Expert Opin Ther Targets. 2013 Aug;17(8):873-8. (PMID: 23862680) Br J Cancer. 2012 Jan 3;106(1):166-73. (PMID: 22095224) Clin Cancer Res. 1996 Sep;2(9):1627-36. (PMID: 9816342) Cancer Res. 2005 Jan 1;65(1):246-53. (PMID: 15665301) Cell. 2009 Feb 20;136(4):763-76. (PMID: 19239894) J Mol Cell Biol. 2015 Apr;7(2):92-104. (PMID: 25735597) Mol Biol Cell. 2005 May;16(5):2395-413. (PMID: 15758027) Wiley Interdiscip Rev RNA. 2012 Jul-Aug;3(4):543-55. (PMID: 22555874) Nature. 1990 Feb 1;343(6257):437-41. (PMID: 2137203) Clin Cancer Res. 2007 Mar 15;13(6):1638-42. (PMID: 17363515) J Struct Biol. 2011 Dec;176(3):370-8. (PMID: 21964468) Nature. 2006 Mar 23;440(7083):556-60. (PMID: 16554823) Nat Struct Mol Biol. 2005 Sep;12(9):772-8. (PMID: 16116436) Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11471-6. (PMID: 8876159) Nucleus. 2014 Sep-Oct;5(5):402-26. (PMID: 25482194) Biochemistry. 2000 Apr 18;39(15):4339-46. (PMID: 10757982) Mol Cell Biol. 2005 Jan;25(1):403-13. (PMID: 15601860) Oncotarget. 2014 Jun 30;5(12):4361-9. (PMID: 24952786) BMC Mol Biol. 2007 Aug 10;8:66. (PMID: 17692122) PLoS One. 2013 Jun 14;8(6):e66436. (PMID: 23799104) Drug Discov Today. 2014 Mar;19(3):259-65. (PMID: 23993916) Nat Rev Mol Cell Biol. 2007 Jul;8(7):574-85. (PMID: 17519961) Nucleus. 2013 Mar-Apr;4(2):134-41. (PMID: 23412654) Proc Natl Acad Sci U S A. 1990 Jan;87(1):147-51. (PMID: 2136950) Mol Biol Cell. 2002 Feb;13(2):579-92. (PMID: 11854414) BMC Cancer. 2005 Sep 12;5:113. (PMID: 16156888) Front Oncol. 2015 Apr 07;5:75. (PMID: 25905039) Acta Pharm. 2005 Sep;55(3):237-49. (PMID: 16375835) J Biol Chem. 2010 Apr 16;285(16):12416-25. (PMID: 20159984) Cells. 2012 Oct 15;1(4):774-98. (PMID: 24710530) Semin Cancer Biol. 2015 Dec;35 Suppl:S244-S275. (PMID: 25865774) Genes Dev. 2003 Jul 15;17(14):1691-702. (PMID: 12865296) J Cell Biol. 1995 Jun;129(5):1181-93. (PMID: 7539809) Int J Mol Sci. 2011;12(3):1595-604. (PMID: 21673909) Cancer Cell. 2012 Jul 10;22(1):51-65. (PMID: 22789538) Nat Chem Biol. 2008 Mar;4(3):203-13. (PMID: 18246061) Anticancer Res. 2014 Feb;34(2):651-8. (PMID: 24510995) Arch Pharm (Weinheim). 1975 Mar;308(3):179-85. (PMID: 1130955) Mol Biol Cell. 2008 Dec;19(12):5296-308. (PMID: 18799616) Cancer Res. 2011 Feb 15;71(4):1418-30. (PMID: 21159662) Cancer Cell. 2014 Jan 13;25(1):77-90. (PMID: 24434211) Pancreas. 2011 Jul;40(5):730-9. (PMID: 21633318) Mol Biol Cell. 2011 Mar 15;22(6):858-67. (PMID: 21233287) Annu Rev Pharmacol Toxicol. 2010;50:131-56. (PMID: 20055700) Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):null. (PMID: 21106648) Mol Cell. 2010 Oct 22;40(2):216-27. (PMID: 20965417) PLoS Biol. 2010 Oct 26;8(10):e1000522. (PMID: 21048991) Oncotarget. 2015 Dec 22;6(41):43620-34. (PMID: 26498364) Nat Protoc. 2006;1(2):729-48. (PMID: 17406303) J Mol Biol. 1984 Oct 5;178(4):897-919. (PMID: 6092647) Cold Spring Harb Symp Quant Biol. 2010;75:599-605. (PMID: 21289045) EMBO J. 1991 Nov;10(11):3467-81. (PMID: 1833187) |
| 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 |