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Warburg Effect

MedGen UID:
275623
•Concept ID:
C1520120
•
Cell or Molecular Dysfunction

Definition

This effect refers to the high cellular levels of lactic acid in tumor cells, and is named after Otto Warburg who worked on photosynthesis. Tumor cells use excessive glucose in their rapid growth, and lactic acid is a product of the glycolytic pathway. This process is not inhibited by oxygen, therefore, it is also called aerobic glycolysis. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWarburg Effect

Professional guidelines

PubMed

Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.
Dal Bello S, Valdemarin F, Martinuzzi D, Filippi F, Gigli GL, Valente M
Nutrients 2022 Sep 17;14(18) doi: 10.3390/nu14183851. PMID: 36145228Free PMC Article
Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma.
Poff A, Koutnik AP, Egan KM, Sahebjam S, D'Agostino D, Kumar NB
Semin Cancer Biol 2019 Jun;56:135-148. Epub 2017 Dec 30 doi: 10.1016/j.semcancer.2017.12.011. PMID: 29294371Free PMC Article
Facilitative glucose transporters: Implications for cancer detection, prognosis and treatment.
Barron CC, Bilan PJ, Tsakiridis T, Tsiani E
Metabolism 2016 Feb;65(2):124-39. Epub 2015 Nov 13 doi: 10.1016/j.metabol.2015.10.007. PMID: 26773935

Recent clinical studies

Etiology

Lactate metabolism in human health and disease.
Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang JX, Wang Z, Yu T
Signal Transduct Target Ther 2022 Sep 1;7(1):305. doi: 10.1038/s41392-022-01151-3. PMID: 36050306Free PMC Article
Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.
Luo P, Zhang Q, Zhong TY, Chen JY, Zhang JZ, Tian Y, Zheng LH, Yang F, Dai LY, Zou C, Li ZJ, Liu JH, Wang JG
Mil Med Res 2022 May 20;9(1):22. doi: 10.1186/s40779-022-00381-4. PMID: 35596191Free PMC Article
Could ketogenic diet "starve" cancer? Emerging evidence.
Barrea L, Caprio M, Tuccinardi D, Moriconi E, Di Renzo L, Muscogiuri G, Colao A, Savastano S; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group
Crit Rev Food Sci Nutr 2022;62(7):1800-1821. Epub 2020 Dec 4 doi: 10.1080/10408398.2020.1847030. PMID: 33274644
Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer.
Kasprzak A
Int J Mol Sci 2021 Jun 16;22(12) doi: 10.3390/ijms22126434. PMID: 34208601Free PMC Article
Glutamine Metabolism in Cancer.
Li T, Copeland C, Le A
Adv Exp Med Biol 2021;1311:17-38. doi: 10.1007/978-3-030-65768-0_2. PMID: 34014532Free PMC Article

Diagnosis

Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations.
Lane J, Brown NI, Williams S, Plaisance EP, Fontaine KR
Nutrients 2021 Oct 12;13(10) doi: 10.3390/nu13103562. PMID: 34684564Free PMC Article
Metabolic reprogramming in triple-negative breast cancer.
Wang Z, Jiang Q, Dong C
Cancer Biol Med 2020 Feb 15;17(1):44-59. doi: 10.20892/j.issn.2095-3941.2019.0210. PMID: 32296576Free PMC Article
The Actual Role of LDH as Tumor Marker, Biochemical and Clinical Aspects.
Jurisic V, Radenkovic S, Konjevic G
Adv Exp Med Biol 2015;867:115-24. doi: 10.1007/978-94-017-7215-0_8. PMID: 26530363
HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection.
Tan VP, Miyamoto S
Autophagy 2015;11(6):963-4. doi: 10.1080/15548627.2015.1042195. PMID: 26075878Free PMC Article
The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism.
Lu J, Tan M, Cai Q
Cancer Lett 2015 Jan 28;356(2 Pt A):156-64. Epub 2014 Apr 13 doi: 10.1016/j.canlet.2014.04.001. PMID: 24732809Free PMC Article

Therapy

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.
Luo P, Zhang Q, Zhong TY, Chen JY, Zhang JZ, Tian Y, Zheng LH, Yang F, Dai LY, Zou C, Li ZJ, Liu JH, Wang JG
Mil Med Res 2022 May 20;9(1):22. doi: 10.1186/s40779-022-00381-4. PMID: 35596191Free PMC Article
The Potential Health Benefits of the Ketogenic Diet: A Narrative Review.
Dowis K, Banga S
Nutrients 2021 May 13;13(5) doi: 10.3390/nu13051654. PMID: 34068325Free PMC Article
Fat and Furious: Lipid Metabolism in Antitumoral Therapy Response and Resistance.
Bacci M, Lorito N, Smiriglia A, Morandi A
Trends Cancer 2021 Mar;7(3):198-213. Epub 2020 Dec 16 doi: 10.1016/j.trecan.2020.10.004. PMID: 33281098
Metabolic reprogramming in triple-negative breast cancer.
Wang Z, Jiang Q, Dong C
Cancer Biol Med 2020 Feb 15;17(1):44-59. doi: 10.20892/j.issn.2095-3941.2019.0210. PMID: 32296576Free PMC Article
How the Warburg effect supports aggressiveness and drug resistance of cancer cells?
Icard P, Shulman S, Farhat D, Steyaert JM, Alifano M, Lincet H
Drug Resist Updat 2018 May;38:1-11. Epub 2018 Mar 20 doi: 10.1016/j.drup.2018.03.001. PMID: 29857814

Prognosis

TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling.
Liu W, Zhao Y, Wang G, Feng S, Ge X, Ye W, Wang Z, Zhu Y, Cai W, Bai J, Zhou X
Redox Biol 2022 Jul;53:102344. Epub 2022 May 18 doi: 10.1016/j.redox.2022.102344. PMID: 35636015Free PMC Article
Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer.
Jiang H, Wei H, Wang H, Wang Z, Li J, Ou Y, Xiao X, Wang W, Chang A, Sun W, Zhao L, Yang S
Cell Death Dis 2022 Mar 4;13(3):206. doi: 10.1038/s41419-022-04632-z. PMID: 35246504Free PMC Article
Could ketogenic diet "starve" cancer? Emerging evidence.
Barrea L, Caprio M, Tuccinardi D, Moriconi E, Di Renzo L, Muscogiuri G, Colao A, Savastano S; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group
Crit Rev Food Sci Nutr 2022;62(7):1800-1821. Epub 2020 Dec 4 doi: 10.1080/10408398.2020.1847030. PMID: 33274644
Targeting Tumor Microenvironment for Cancer Therapy.
Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR
Int J Mol Sci 2019 Feb 15;20(4) doi: 10.3390/ijms20040840. PMID: 30781344Free PMC Article
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.
Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W, Gao X, Aldape K, Lu Z
Nature 2011 Dec 1;480(7375):118-22. doi: 10.1038/nature10598. PMID: 22056988Free PMC Article

Clinical prediction guides

Glucose Metabolism in Cancer.
Bose S, Le A
Adv Exp Med Biol 2018;1063:3-12. doi: 10.1007/978-3-319-77736-8_1. PMID: 29946772
Transcriptional Regulation of the Warburg Effect in Cancer by SIX1.
Li L, Liang Y, Kang L, Liu Y, Gao S, Chen S, Li Y, You W, Dong Q, Hong T, Yan Z, Jin S, Wang T, Zhao W, Mai H, Huang J, Han X, Ji Q, Song Q, Yang C, Zhao S, Xu X, Ye Q
Cancer Cell 2018 Mar 12;33(3):368-385.e7. Epub 2018 Feb 15 doi: 10.1016/j.ccell.2018.01.010. PMID: 29455928
The Warburg Effect: How Does it Benefit Cancer Cells?
Liberti MV, Locasale JW
Trends Biochem Sci 2016 Mar;41(3):211-218. Epub 2016 Jan 5 doi: 10.1016/j.tibs.2015.12.001. PMID: 26778478Free PMC Article
Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression.
Li Z, Zhang H
Cell Mol Life Sci 2016 Jan;73(2):377-92. Epub 2015 Oct 23 doi: 10.1007/s00018-015-2070-4. PMID: 26499846
Otto Warburg's contributions to current concepts of cancer metabolism.
Koppenol WH, Bounds PL, Dang CV
Nat Rev Cancer 2011 May;11(5):325-37. Epub 2011 Apr 14 doi: 10.1038/nrc3038. PMID: 21508971

Recent systematic reviews

Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.
Silva A, Cerqueira MC, Rosa B, Sobral C, Pinto-Ribeiro F, Costa MF, Baltazar F, Afonso J
Int J Mol Sci 2023 Mar 7;24(6) doi: 10.3390/ijms24065141. PMID: 36982217Free PMC Article
Molecular prognostic indicators in HPV-positive oropharyngeal cancer: an updated review.
Morand GB, Diaconescu A, Ibrahim I, Lamarche G, Ruas JS, Dalfen J, Hier MP, Alaoui-Jamali MA, Maschietto M, da Silva SD
Clin Exp Metastasis 2022 Jun;39(3):407-416. Epub 2022 Jan 27 doi: 10.1007/s10585-022-10148-9. PMID: 35084607
The Role of Glucose Transporters in Oral Squamous Cell Carcinoma.
Botha H, Farah CS, Koo K, Cirillo N, McCullough M, Paolini R, Celentano A
Biomolecules 2021 Jul 21;11(8) doi: 10.3390/biom11081070. PMID: 34439735Free PMC Article
Role of ketogenic metabolic therapy in malignant glioma: A systematic review.
Winter SF, Loebel F, Dietrich J
Crit Rev Oncol Hematol 2017 Apr;112:41-58. Epub 2017 Feb 20 doi: 10.1016/j.critrevonc.2017.02.016. PMID: 28325264
Glucose metabolic phenotype of pancreatic cancer.
Chan AK, Bruce JI, Siriwardena AK
World J Gastroenterol 2016 Mar 28;22(12):3471-85. doi: 10.3748/wjg.v22.i12.3471. PMID: 27022229Free PMC Article

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