دورية أكاديمية
أعرض في EDS

p53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect.

التفاصيل البيبلوغرافية
العنوان: p53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect.
المؤلفون: Abukwaik R; Mathematics Department, King Abdulaziz University, Rabigh, Saudi Arabia. rabukwaik@kau.edu.sa.; School of Mathematics, University of Birmingham, Birmingham, B15 2TS, UK. rabukwaik@kau.edu.sa., Vera-Siguenza E; School of Mathematics, University of Birmingham, Birmingham, B15 2TS, UK.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK., Tennant D; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK., Spill F; School of Mathematics, University of Birmingham, Birmingham, B15 2TS, UK. f.spill@bham.ac.uk.
المصدر: Bulletin of mathematical biology [Bull Math Biol] 2024 Aug 29; Vol. 86 (10), pp. 124. Date of Electronic Publication: 2024 Aug 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 0401404 Publication Model: Electronic Cited Medium: Internet ISSN: 1522-9602 (Electronic) Linking ISSN: 00928240 NLM ISO Abbreviation: Bull Math Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Springer
Original Publication: New York, Pergamon Press.
مواضيع طبية MeSH: Tumor Suppressor Protein p53*/metabolism , Tumor Suppressor Protein p53*/genetics , Oxidative Phosphorylation* , Glycolysis* , Warburg Effect, Oncologic* , Models, Biological* , Mathematical Concepts* , Computer Simulation* , Mutation* , Colonic Neoplasms*/metabolism , Colonic Neoplasms*/genetics , Colonic Neoplasms*/pathology, Humans ; Glucose/metabolism ; Apoptosis ; Signal Transduction ; Neoplasms/metabolism ; Neoplasms/genetics ; Neoplasms/pathology ; Cell Line, Tumor ; Mitochondria/metabolism
مستخلص: Cancer cells exhibit significant alterations in their metabolism, characterised by a reduction in oxidative phosphorylation (OXPHOS) and an increased reliance on glycolysis, even in the presence of oxygen. This metabolic shift, known as the Warburg effect, is pivotal in fuelling cancer's uncontrolled growth, invasion, and therapeutic resistance. While dysregulation of many genes contributes to this metabolic shift, the tumour suppressor gene p53 emerges as a master player. Yet, the molecular mechanisms remain elusive. This study introduces a comprehensive mathematical model, integrating essential p53 targets, offering insights into how p53 orchestrates its targets to redirect cancer metabolism towards an OXPHOS-dominant state. Simulation outcomes align closely with experimental data comparing glucose metabolism in colon cancer cells with wild-type and mutated p53. Additionally, our findings reveal the dynamic capability of elevated p53 activation to fully reverse the Warburg effect, highlighting the significance of its activity levels not just in triggering apoptosis (programmed cell death) post-chemotherapy but also in modifying the metabolic pathways implicated in treatment resistance. In scenarios of p53 mutations, our analysis suggests targeting glycolysis-instigating signalling pathways as an alternative strategy, whereas targeting solely synthesis of cytochrome c oxidase 2 (SCO2) does support mitochondrial respiration but may not effectively suppress the glycolysis pathway, potentially boosting the energy production and cancer cell viability.
(© 2024. The Author(s).)
References: Sci Rep. 2020 Dec 14;10(1):21940. (PMID: 33318678)
Placenta. 2013 Oct;34(10):953-8. (PMID: 23886770)
Biochem Biophys Res Commun. 2001 Sep 21;287(2):562-7. (PMID: 11554766)
Cancer Res. 2000 Mar 15;60(6):1541-5. (PMID: 10749120)
Science. 2006 Jun 16;312(5780):1650-3. (PMID: 16728594)
J Oncol. 2012;2012:951724. (PMID: 22481935)
PLoS One. 2012;7(2):e32035. (PMID: 22363791)
Genes Dev. 2004 Dec 1;18(23):2893-904. (PMID: 15545625)
Biochim Biophys Acta. 2013 Apr;1835(2):164-9. (PMID: 23266512)
Plant Physiol. 1977 May;59(5):842-8. (PMID: 16659953)
J Proteome Res. 2019 Aug 2;18(8):3142-3155. (PMID: 31293153)
Biochem J. 2004 May 15;380(Pt 1):289-95. (PMID: 14992692)
Antioxid Redox Signal. 2011 Sep 15;15(6):1739-48. (PMID: 20919942)
Am J Vet Res. 2008 Aug;69(8):1091-6. (PMID: 18672976)
Mol Cancer Ther. 2013 Nov;12(11):2319-30. (PMID: 24170767)
J Vet Emerg Crit Care (San Antonio). 2018 Mar;28(2):85-105. (PMID: 29533512)
J Biol Chem. 2002 Feb 15;277(7):5484-9. (PMID: 11729185)
Cancer Lett. 2015 Jan 28;356(2 Pt A):165-70. (PMID: 24486219)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
J Biol Chem. 2004 Apr 16;279(16):16606-13. (PMID: 14764604)
Acta Pharmacol Sin. 2010 Sep;31(9):1208-12. (PMID: 20729871)
Oncotarget. 2017 Jul 11;8(28):46363-46380. (PMID: 28624784)
Cancer Res. 1999 Nov 15;59(22):5830-5. (PMID: 10582706)
Methods Mol Biol. 2021;2310:271-285. (PMID: 34096008)
Biochem J. 1998 Aug 1;333 ( Pt 3):713-8. (PMID: 9677332)
Cell Adh Migr. 2013 Sep-Oct;7(5):395-403. (PMID: 24131935)
Oncotarget. 2016 Jun 28;7(26):40621-40629. (PMID: 27259254)
Oncotarget. 2018 May 4;9(34):23780-23823. (PMID: 29805774)
PLoS One. 2015 Jul 06;10(7):e0131663. (PMID: 26147621)
Nat Commun. 2020 Jan 3;11(1):102. (PMID: 31900386)
Biochem Biophys Res Commun. 2007 Sep 21;361(2):468-73. (PMID: 17658463)
Science. 2009 Aug 28;325(5944):1134-8. (PMID: 19713527)
Cells. 2023 Jun 08;12(12):. (PMID: 37371055)
Biochem J. 1966 Sep;100(3):739-44. (PMID: 16742416)
J Theor Biol. 2023 Sep 7;572:111562. (PMID: 37348784)
Nat Rev Drug Discov. 2005 Dec;4(12):988-1004. (PMID: 16341064)
Science. 2011 Jun 17;332(6036):1433-5. (PMID: 21680840)
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5367-72. (PMID: 11959990)
J Biol Chem. 1983 Feb 25;258(4):2315-20. (PMID: 6822563)
Mol Cancer Ther. 2019 Oct;18(10):1673-1681. (PMID: 31511353)
Biochim Biophys Acta. 2015 Jan;1855(1):104-21. (PMID: 25450577)
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6048-53. (PMID: 9177166)
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16584-9. (PMID: 18931307)
Mol Cell. 2001 Aug;8(2):317-25. (PMID: 11545734)
J Mol Cell Biol. 2019 Apr 1;11(4):284-292. (PMID: 30500901)
Oncogene. 2012 Aug 16;31(33):3764-76. (PMID: 22120717)
Metabolites. 2017 May 20;7(2):. (PMID: 28531108)
Arch Biochem Biophys. 1991 Feb 1;284(2):285-91. (PMID: 1989512)
Mol Cell Biol. 2001 Jun;21(12):3995-4004. (PMID: 11359907)
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11598-603. (PMID: 11504915)
Nat Cell Biol. 2008 May;10(5):611-8. (PMID: 18391940)
Cancers (Basel). 2021 Mar 24;13(7):. (PMID: 33804985)
PLoS One. 2013;8(1):e55298. (PMID: 23383143)
Biochem J. 1993 Mar 15;290 ( Pt 3):913-9. (PMID: 8457217)
Front Bioeng Biotechnol. 2021 Jun 02;9:678038. (PMID: 34150734)
Mol Syst Biol. 2011 May 10;7:488. (PMID: 21556066)
Mol Cell. 2010 Jul 30;39(2):171-83. (PMID: 20670887)
Mol Cell Biol. 2011 Dec;31(24):4938-50. (PMID: 21969607)
Protein Cell. 2014;5(8):592-602. (PMID: 25015087)
Cell Death Differ. 2010 Feb;17(2):255-67. (PMID: 19927155)
J Biol Chem. 2014 Sep 5;289(36):25227-40. (PMID: 24990947)
Front Oncol. 2014 Sep 23;4:252. (PMID: 25295225)
Am J Clin Nutr. 2011 Apr;93(4):891S-6. (PMID: 21325438)
Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):251-62. (PMID: 22436748)
Cell. 2008 Aug 8;134(3):451-60. (PMID: 18692468)
Mol Ther. 2019 Oct 2;27(10):1810-1824. (PMID: 31208913)
Acta Pharmacol Sin. 2021 Oct;42(10):1547-1555. (PMID: 33510458)
Cancer Res. 2004 Apr 1;64(7):2627-33. (PMID: 15059920)
J Biomed Res. 2013 Jul;27(4):254-71. (PMID: 23885265)
Nat Rev Cancer. 2011 Feb;11(2):85-95. (PMID: 21258394)
J Cell Sci. 2003 Apr 1;116(Pt 7):1319-26. (PMID: 12615973)
Mol Cell Biol. 2006 May;26(9):3514-26. (PMID: 16611993)
Proc Natl Acad Sci U S A. 2017 May 23;114(21):5337-5342. (PMID: 28484034)
Blood. 2011 Jan 13;117(2):591-4. (PMID: 20959606)
Recent Results Cancer Res. 2016;207:39-72. (PMID: 27557534)
Mol Imaging. 2015;14:490-8. (PMID: 26461458)
Oncogene. 2020 Jan;39(2):469-485. (PMID: 31597953)
Am J Physiol. 1995 Jun;268(6 Pt 1):G879-88. (PMID: 7611409)
Mol Cell Biol. 2006 May;26(10):3955-65. (PMID: 16648488)
Oncol Rep. 2016 Mar;35(3):1281-6. (PMID: 26675982)
Nat Cell Biol. 2002 Sep;4(9):648-57. (PMID: 12172553)
Eur J Biochem. 2001 May;268(10):2773-8. (PMID: 11358491)
Am J Pathol. 2011 Sep;179(3):1405-14. (PMID: 21763680)
Metabolites. 2015 Sep 30;5(4):571-600. (PMID: 26437434)
Biosci Rep. 2021 Apr 30;41(4):. (PMID: 33739396)
Biophys J. 2009 Jul 22;97(2):415-34. (PMID: 19619456)
Hum Mol Genet. 2008 Oct 1;17(19):2934-48. (PMID: 18614546)
Eur J Biochem. 2001 May;268(10):2779-83. (PMID: 11358492)
Biosci Rep. 2002 Oct-Dec;22(5-6):501-11. (PMID: 12635847)
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14266-71. (PMID: 16186499)
Nat Rev Cancer. 2009 Oct;9(10):691-700. (PMID: 19759539)
Cell. 2003 Nov 26;115(5):577-90. (PMID: 14651849)
Proc Natl Acad Sci U S A. 2011 May 31;108(22):8990-5. (PMID: 21576488)
Cells. 2021 Feb 10;10(2):. (PMID: 33578751)
Mol Syst Biol. 2014 Aug 01;10:744. (PMID: 25086087)
Int J Cancer. 2019 Feb 15;144(4):674-686. (PMID: 30121950)
Microbiology (Reading). 2012 May;158(Pt 5):1350-1358. (PMID: 22343352)
Cell Biosci. 2013 Feb 06;3(1):9. (PMID: 23388203)
Biophys J. 2006 Aug 1;91(3):857-65. (PMID: 16648169)
J Physiol Sci. 2020 Sep 22;70(1):44. (PMID: 32962633)
Br J Cancer. 2014 Apr 15;110(8):2081-9. (PMID: 24619078)
Chembiochem. 2020 Jan 15;21(1-2):45-52. (PMID: 31553512)
J Biol Chem. 2005 Jul 15;280(28):25953-9. (PMID: 15843377)
J Cancer. 2016 Apr 26;7(7):817-22. (PMID: 27162540)
Brain Pathol. 2016 Jan;26(1):3-17. (PMID: 26269128)
EMBO J. 1998 Nov 16;17(22):6573-86. (PMID: 9822602)
Mol Endocrinol. 2005 May;19(5):1304-17. (PMID: 15695372)
Mol Cell Biol. 2002 Oct;22(20):7004-14. (PMID: 12242281)
Trends Cell Biol. 2010 Jul;20(7):427-34. (PMID: 20399660)
EMBO J. 1993 Feb;12(2):461-8. (PMID: 8440237)
Cell Metab. 2006 Mar;3(3):177-85. (PMID: 16517405)
Oncotarget. 2015 Apr 10;6(10):7365-78. (PMID: 25812084)
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188568. (PMID: 34023419)
J Biol Chem. 2004 Feb 13;279(7):5072-80. (PMID: 14615477)
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4675-80. (PMID: 20176937)
Cell. 1995 Oct 6;83(1):69-78. (PMID: 7553875)
Cell Death Dis. 2015 Aug 06;6:e1842. (PMID: 26247727)
Nature. 1997 May 15;387(6630):296-9. (PMID: 9153395)
Diabetes. 2002 Feb;51(2):276-83. (PMID: 11812733)
Cell Cycle. 2007 Jan 1;6(1):85-94. (PMID: 17245126)
Cell. 2006 Jul 14;126(1):107-20. (PMID: 16839880)
FEBS J. 2018 Aug;285(16):2926-2943. (PMID: 29893496)
Mol Cell Biol. 2008 Aug;28(16):5106-19. (PMID: 18559422)
Cancer Cell Int. 2015 Feb 15;15:19. (PMID: 25705126)
Redox Biol. 2021 Sep;45:102058. (PMID: 34218200)
J Biol Chem. 2017 Jan 6;292(1):305-312. (PMID: 27856638)
Mol Cell. 2005 Apr 29;18(3):283-93. (PMID: 15866171)
Genes Dev. 2008 Jan 15;22(2):239-51. (PMID: 18198340)
Signal Transduct Target Ther. 2020 Sep 2;5(1):177. (PMID: 32873793)
Cancer Res. 2017 Apr 1;77(7):1564-1574. (PMID: 28202516)
Cancer Treat Rev. 2004 Apr;30(2):193-204. (PMID: 15023437)
معلومات مُعتمدة: MR/T043571/1 United Kingdom MRC_ Medical Research Council; C42109/A26982 United Kingdom CRUK_ Cancer Research UK; C42109/A24747 United Kingdom CRUK_ Cancer Research UK; EP/N014391/2 Engineering and Physical Sciences Research Council
فهرسة مساهمة: Keywords: Cancer metabolism; Glycolysis; Hypoxia; Mathematical biology; Warburg effect; p53
المشرفين على المادة: 0 (Tumor Suppressor Protein p53)
0 (TP53 protein, human)
IY9XDZ35W2 (Glucose)
تواريخ الأحداث: Date Created: 20240829 Date Completed: 20240829 Latest Revision: 20240903
رمز التحديث: 20240903
مُعرف محوري في PubMed: PMC11362376
DOI: 10.1007/s11538-024-01346-5
PMID: 39207627
قاعدة البيانات: MEDLINE
الوصف
تدمد:1522-9602
DOI:10.1007/s11538-024-01346-5