دورية أكاديمية
WWOX promotes osteosarcoma development via upregulation of Myc.
| العنوان: | WWOX promotes osteosarcoma development via upregulation of Myc. |
|---|---|
| المؤلفون: | Akkawi R; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Hidmi O; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Haj-Yahia A; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Monin J; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Diment J; Department of Pathology, Hadassah University Medical Center, Jerusalem, Israel., Drier Y; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Stein GS; Department of Biochemistry, Larner College of Medicine, UVM Cancer Center, University of Vermont, Burlington, VT, USA., Aqeilan RI; The Concern Foundation Laboratories, The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. ramiaq@mail.huji.ac.il.; Cyprus Cancer Research Institute (CCRI), Nicosia, Cyprus. ramiaq@mail.huji.ac.il. |
| المصدر: | Cell death & disease [Cell Death Dis] 2024 Jan 05; Vol. 15 (1), pp. 13. Date of Electronic Publication: 2024 Jan 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group |
| مواضيع طبية MeSH: | Bone Neoplasms*/genetics , Osteosarcoma*/genetics , WW Domain-Containing Oxidoreductase*/genetics , WW Domain-Containing Oxidoreductase*/metabolism , Proto-Oncogene Proteins c-myc*/genetics , Proto-Oncogene Proteins c-myc*/metabolism, Animals ; Humans ; Mice ; Tumor Suppressor Proteins/genetics ; Up-Regulation/genetics |
| مستخلص: | Osteosarcoma is an aggressive bone tumor that primarily affects children and adolescents. This malignancy is highly aggressive, associated with poor clinical outcomes, and primarily metastasizes to the lungs. Due to its rarity and biological heterogeneity, limited studies on its molecular basis exist, hindering the development of effective therapies. The WW domain-containing oxidoreductase (WWOX) is frequently altered in human osteosarcoma. Combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate osteosarcoma development. In this study, we generated a traceable osteosarcoma mouse model harboring the deletion of Trp53 alone (single-knockout) or combined deletion of Wwox/Trp53 (double-knockout) and expressing a tdTomato reporter. By tracking Tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow mesenchymal stem cells of non-osteosarcoma-bearing mice (young BM). We found that double-knockout young BM cells, but not single-knockout young BM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these double-knockout young BM cells revealed their resemblance to osteosarcoma tumor cells. Interestingly, one of the observed significant transcriptomic changes in double-knockout young BM cells was the upregulation of Myc and its target genes compared to single-knockout young BM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing revealed its increased enrichment on Myc targets, which were upregulated in double-knockout young BM cells. Restoration of WWOX in double-knockout young BM cells reduced Myc protein levels. As a prototype target, we demonstrated the upregulation of MCM7, a known Myc target, in double-knockout young BM relative to single-knockout young BM cells. Inhibition of MCM7 expression using simvastatin resulted in reduced proliferation and tumor cell growth of double-knockout young BM cells. Our findings reveal BM mesenchymal stem cells as a platform to study osteosarcoma and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis. (© 2024. The Author(s).) |
| التعليقات: | Erratum in: Cell Death Dis. 2024 Feb 14;15(2):141. (PMID: 38355659) |
| References: | Nat Rev Cancer. 2002 Oct;2(10):764-76. (PMID: 12360279) Oncogene. 2013 Oct 10;32(41):4970-80. (PMID: 23222711) Science. 2002 Jul 5;297(5578):102-4. (PMID: 12098700) J Biol Chem. 2015 Nov 20;290(47):28070-28083. (PMID: 26378234) Cell Death Dis. 2022 Dec 27;13(12):1074. (PMID: 36572673) Cancer Res. 2016 Oct 15;76(20):6107-6117. (PMID: 27550453) Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11851-6. (PMID: 18697945) Oncology. 1998 Nov-Dec;55(6):556-63. (PMID: 9778623) Stem Cells Transl Med. 2017 Feb;6(2):512-526. (PMID: 28191765) Elife. 2020 Aug 05;9:. (PMID: 32755539) Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8956-61. (PMID: 18579778) Bone. 2014 May;62:56-63. (PMID: 24530473) EMBO Mol Med. 2021 Aug 9;13(8):e13610. (PMID: 34268881) Curr Top Microbiol Immunol. 2006;302:169-203. (PMID: 16620029) Sarcoma. 2012;2012:627254. (PMID: 22685381) Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4716-25. (PMID: 25331887) Methods Mol Biol. 2022;2535:131-140. (PMID: 35867228) Cancer Lett. 2013 Feb 1;329(1):9-16. (PMID: 22960596) Nat Commun. 2022 Nov 23;13(1):7207. (PMID: 36418292) J Bone Miner Res. 2010 Apr;25(4):683-91. (PMID: 20205169) Genes Dev. 2008 Jun 15;22(12):1662-76. (PMID: 18559481) Cell Rep. 2014 Apr 10;7(1):104-12. (PMID: 24703847) N Engl J Med. 2005 May 26;352(21):2184-92. (PMID: 15917383) Haematologica. 2007 May;92(5):682-5. (PMID: 17488694) J Cell Physiol. 2007 Aug;212(2):307-10. (PMID: 17458891) Nature. 2023 May;617(7959):147-153. (PMID: 36949200) Hum Mol Genet. 2001 Apr;10(7):699-703. (PMID: 11257102) Future Oncol. 2010 Feb;6(2):249-59. (PMID: 20146584) J Immunol. 2000 Sep 1;165(5):2712-8. (PMID: 10946302) Cancer. 2009 Apr 1;115(7):1531-43. (PMID: 19197972) Sci Rep. 2017 Feb 02;7:41776. (PMID: 28150753) Cell Death Dis. 2018 Aug 6;9(8):832. (PMID: 30082886) Nat Rev Cancer. 2014 Nov;14(11):722-35. (PMID: 25319867) Sarcoma. 2011;2011:679457. (PMID: 21253504) Cancer Res. 2010 Jul 1;70(13):5577-86. (PMID: 20530675) Mol Cancer. 2011 May 28;10:65. (PMID: 21619671) Pharmacol Ther. 2013 Jan;137(1):89-99. (PMID: 22983152) PLoS One. 2016 May 11;11(5):e0152621. (PMID: 27167624) J Cell Biochem. 2009 Nov 1;108(4):737-45. (PMID: 19708029) N Engl J Med. 2012 Nov 8;367(19):1792-802. (PMID: 23134381) Ann Oncol. 2014 Sep;25 Suppl 3:iii113-23. (PMID: 25210081) Genes Cancer. 2017 Jan;8(1-2):484-494. (PMID: 28435520) PLoS One. 2014 Jan 15;9(1):e85161. (PMID: 24454809) Clin Cancer Res. 2010 Aug 15;16(16):4256-67. (PMID: 20610556) Oncogene. 2022 Jan;41(5):683-691. (PMID: 34803166) Cell Cycle. 2007 Jan 15;6(2):205-17. (PMID: 17314511) BMC Cancer. 2008 Jan 16;8:9. (PMID: 18199328) Nature. 1990 Feb 1;343(6257):425-30. (PMID: 1967820) Endocrinology. 1997 May;138(5):2109-16. (PMID: 9112411) Front Mol Biosci. 2021 Jun 22;8:668402. (PMID: 34239894) Mol Cell. 1999 Aug;4(2):199-207. (PMID: 10488335) Cell Death Dis. 2018 May 3;9(5):511. (PMID: 29724996) Br J Haematol. 2010 May;149(4):484-97. (PMID: 20346013) Bone Res. 2023 Jan 2;11(1):1. (PMID: 36588108) Oncotarget. 2016 Jul 26;7(30):46835-46847. (PMID: 27206675) Anal Cell Pathol (Amst). 2020 Feb 3;2020:3750294. (PMID: 32089988) Nature. 2007 Jul 26;448(7152):445-51. (PMID: 17597761) Cell Death Dis. 2017 Mar 16;8(3):e2673. (PMID: 28300827) Cancer Res. 2019 Apr 15;79(8):1784-1798. (PMID: 30622118) J Natl Cancer Inst. 2003 Jun 18;95(12):844-6. (PMID: 12813163) |
| معلومات مُعتمدة: | 682118 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); 2017269 United States - Israel Binational Science Foundation (BSF); 2017269 United States - Israel Binational Science Foundation (BSF) |
| المشرفين على المادة: | 0 (tdTomato) 0 (Tumor Suppressor Proteins) EC 1.1.1.- (WW Domain-Containing Oxidoreductase) EC 1.1.1.- (WWOX protein, human) EC 1.1.1.- (Wwox protein, mouse) 0 (Myc protein, mouse) 0 (Proto-Oncogene Proteins c-myc) |
| تواريخ الأحداث: | Date Created: 20240105 Date Completed: 20240126 Latest Revision: 20240217 |
| رمز التحديث: | 20240217 |
| مُعرف محوري في PubMed: | PMC10770339 |
| DOI: | 10.1038/s41419-023-06378-8 |
| PMID: | 38182577 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2041-4889 |
|---|---|
| DOI: | 10.1038/s41419-023-06378-8 |