دورية أكاديمية
Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer.
| العنوان: | Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer. |
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| المؤلفون: | Cargill KR; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Stewart CA; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Park EM; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ramkumar K; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gay CM; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cardnell RJ; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang Q; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Diao L; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Shen L; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Fan YH; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chan WK; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lorenzi PL; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Oliver TG; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Wang J; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Byers LA; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. lbyers@mdanderson.org. |
| المصدر: | Cancer & metabolism [Cancer Metab] 2021 Sep 23; Vol. 9 (1), pp. 33. Date of Electronic Publication: 2021 Sep 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101607582 Publication Model: Electronic Cited Medium: Print ISSN: 2049-3002 (Print) Linking ISSN: 20493002 NLM ISO Abbreviation: Cancer Metab Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, 2013- |
| مستخلص: | Introduction: The transcription factor MYC is overexpressed in 30% of small cell lung cancer (SCLC) tumors and is known to modulate the balance between two major pathways of metabolism: glycolysis and mitochondrial respiration. This duality of MYC underscores the importance of further investigation into its role in SCLC metabolism and could lead to insights into metabolic targeting approaches. Methods: We investigated differences in metabolic pathways in transcriptional and metabolomics datasets based on cMYC expression in patient and cell line samples. Metabolic pathway utilization was evaluated by flow cytometry and Seahorse extracellular flux methodology. Glycolysis inhibition was evaluated in vitro and in vivo using PFK158, a small molecular inhibitor of PFKFB3. Results: MYC-overexpressing SCLC patient samples and cell lines exhibited increased glycolysis gene expression directly mediated by MYC. Further, MYC-overexpressing cell lines displayed enhanced glycolysis consistent with the Warburg effect, while cell lines with low MYC expression appeared more reliant on oxidative metabolism. Inhibition of glycolysis with PFK158 preferentially attenuated glucose uptake, ATP production, and lactate in MYC-overexpressing cell lines. Treatment with PFK158 in xenografts delayed tumor growth and decreased glycolysis gene expression. Conclusions: Our study highlights an in-depth characterization of SCLC metabolic programming and presents glycolysis as a targetable mechanism downstream of MYC that could offer therapeutic benefit in a subset of SCLC patients. (© 2021. The Author(s).) |
| References: | Exp Mol Med. 2020 Feb;52(2):192-203. (PMID: 32060354) J Immunol. 2017 Feb 1;198(3):999-1005. (PMID: 28115589) J Thorac Oncol. 2020 Feb;15(2):274-287. (PMID: 31655296) Cancer Res. 1985 Jun;45(6):2924-30. (PMID: 2985258) Signal Transduct Target Ther. 2020 Jul 10;5(1):124. (PMID: 32651356) Mol Cell Biol. 2004 Jul;24(13):5923-36. (PMID: 15199147) Oxid Med Cell Longev. 2019 Jun 25;2019:7346492. (PMID: 31341534) Cancer Cell. 2020 Jul 13;38(1):60-78.e12. (PMID: 32473656) Clin Cancer Res. 2019 Aug 15;25(16):5107-5121. (PMID: 31164374) N Engl J Med. 2018 Dec 6;379(23):2220-2229. (PMID: 30280641) Oncotarget. 2017 Jul 25;8(30):49275-49292. (PMID: 28525376) Cell Death Dis. 2019 Sep 27;10(10):725. (PMID: 31562297) Cell. 2017 Oct 5;171(2):358-371.e9. (PMID: 28985563) Mol Cell. 2019 Dec 5;76(5):838-851.e5. (PMID: 31564558) Nat Med. 2016 Apr;22(4):427-32. (PMID: 26950360) Blood. 2007 May 1;109(9):3812-9. (PMID: 17255361) Bioinformatics. 2015 May 15;31(10):1692-4. (PMID: 25600946) Cell. 2015 Sep 10;162(6):1229-41. (PMID: 26321679) Oncotarget. 2017 Sep 1;8(43):73419-73432. (PMID: 29088717) Oncotarget. 2017 Sep 6;8(43):75206-75216. (PMID: 29088858) Lancet Oncol. 2016 Jul;17(7):883-895. (PMID: 27269741) Signal Transduct Target Ther. 2018 Feb 23;3:5. (PMID: 29527331) Cell Metab. 2018 Sep 4;28(3):369-382.e5. (PMID: 30043754) Thorac Cancer. 2015 Jan;6(1):17-24. (PMID: 26273330) PLoS One. 2016 Apr 07;11(4):e0152584. (PMID: 27055253) Front Oncol. 2017 Aug 28;7:193. (PMID: 28894699) Cancer Cell. 2021 Mar 8;39(3):346-360.e7. (PMID: 33482121) Nat Med. 2019 May;25(5):850-860. (PMID: 31068703) Cancer Cell. 2017 Feb 13;31(2):270-285. (PMID: 28089889) J Clin Invest. 1987 Jun;79(6):1629-34. (PMID: 3034978) Radiother Oncol. 2009 Sep;92(3):329-33. (PMID: 19604589) Int J Cancer. 2019 Jan 1;144(1):178-189. (PMID: 30226266) J Clin Invest. 2021 Jan 4;131(1):. (PMID: 33079728) J Biol Chem. 2019 Jun 14;294(24):9615-9630. (PMID: 31040177) Nat Rev Cancer. 2019 May;19(5):289-297. (PMID: 30926931) Cell. 2015 Sep 10;162(6):1217-28. (PMID: 26321681) Cell Cycle. 2011 Aug 15;10(16):2806-15. (PMID: 21822053) Nat Genet. 2012 Oct;44(10):1104-10. (PMID: 22941188) Cold Spring Harb Perspect Med. 2014 Jun 02;4(6):. (PMID: 24890832) Trends Biochem Sci. 2010 Aug;35(8):427-33. (PMID: 20570523) Cancer Cell. 2003 Sep;4(3):181-9. (PMID: 14522252) Nutr Metab (Lond). 2010 Jan 27;7:7. (PMID: 20181022) Free Radic Res. 2010 May;44(5):479-96. (PMID: 20370557) Cell. 2012 Mar 30;149(1):22-35. (PMID: 22464321) Semin Cell Dev Biol. 2020 Feb;98:54-62. (PMID: 31238096) Front Oncol. 2020 May 15;10:776. (PMID: 32500033) Biochim Biophys Acta. 2016 Oct;1863(10):2422-35. (PMID: 26828774) Nat Rev Drug Discov. 2019 Sep;18(9):669-688. (PMID: 31363227) Nature. 2015 Aug 6;524(7563):47-53. (PMID: 26168399) Sci Rep. 2013;3:1911. (PMID: 23714854) Methods Mol Biol. 2012;810:183-205. (PMID: 22057568) Oncogene. 1991 Oct;6(10):1775-8. (PMID: 1656362) Clin Cancer Res. 2012 Oct 15;18(20):5546-53. (PMID: 23071356) Front Oncol. 2018 Nov 02;8:500. (PMID: 30456204) Transl Lung Cancer Res. 2016 Aug;5(4):450-1. (PMID: 27676363) Cancer Chemother Pharmacol. 2014 Feb;73(2):417-27. (PMID: 24352250) Cell. 2016 Feb 11;164(4):681-94. (PMID: 26853473) Transl Lung Cancer Res. 2016 Jun;5(3):288-300. (PMID: 27413711) Front Endocrinol (Lausanne). 2018 Apr 12;9:129. (PMID: 29706933) |
| معلومات مُعتمدة: | R01-CA207295 United States CA NCI NIH HHS; U01-CA231844 United States CA NCI NIH HHS; U01-CA235510 United States CA NCI NIH HHS; S10-OD012304-01 United States CA NCI NIH HHS; T32-CA009666 United States CA NCI NIH HHS; R01 CA207295 United States CA NCI NIH HHS; P50 CA070907 United States CA NCI NIH HHS; U01-CA213274 United States CA NCI NIH HHS; R50-CA243698 United States CA NCI NIH HHS; T32 CA009666 United States CA NCI NIH HHS; U01-CA21373 United States CA NCI NIH HHS; U01 CA213273 United States CA NCI NIH HHS; P30 CA016672 United States CA NCI NIH HHS; T32 CA009302 United States CA NCI NIH HHS; P30-CA16672 United States CA NCI NIH HHS; R50 CA243698 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Glycolysis; MYC; Metabolism; PFK158; Small cell lung cancer |
| تواريخ الأحداث: | Date Created: 20210924 Latest Revision: 20220716 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8461854 |
| DOI: | 10.1186/s40170-021-00270-9 |
| PMID: | 34556188 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2049-3002 |
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| DOI: | 10.1186/s40170-021-00270-9 |