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Erken Kanserde Metabolik Yeniden Programlama: Değişmiş Şeker ve Tümör Oluşumundaki Rolü

Yıl 2025, Cilt: 8 Sayı: 2, 117 - 127, 18.07.2025

Öz

Metabolik yeniden programlama, kanserin bir belirteci olup, kanserojenez ve kanser gelişiminin ilk aşamalarında önemli bir rol oynar. Bu fenomen, özellikle tümör büyümesi ve yayılması için gerekli enerji ve yapı taşlarını sağlayan şekerlerin kullanımında olmak üzere, hücresel metabolizmadaki değişiklikleri içerir. Bu inceleme, erken kanserle ilişkili metabolik yeniden programlamaya ve bunun şeker metabolizması üzerindeki etkisine odaklanmaktadır. Kanser hücreleri, Adenozin Trifosfat üretimi ve biyokütle sentezini hızlandıran, genellikle Warburg etkisi olarak bilinen, artmış glukoz alımı ve kullanımını sergiler. Ayrıca, kanser hücreleri artan glikoliz akışı gösterir, glukoz metabolitlerini hücre büyümesini destekleyen anabolik yollara yönlendirir. Onkogenik sinyal yolları, anahtar düzenleyicilerin aktivasyonu ve p53 geni gibi tümör baskılayıcı genlerdeki değişiklikler dahil olmak üzere, şeker metabolizmasındaki bu değişiklikleri yönlendirir. Kanser hücrelerinde şeker metabolizmasının yenilenmesi, tümörün hayatta kalmasını ve ilerlemesini kolaylaştırarak seçici bir avantaj sağlar. Ayrıca, erken evre kanserdeki metabolik değişiklikler, biyosentez, redoks dengesi ve post-translasyonel modifikasyonlar için ara maddelerin oluşumunu teşvik ederek tümör oluşumuna daha fazla katkıda bulunur. Erken kanserde metabolik yeniden programlamanın karmaşıklıklarını anlamak, metabolik zayıflıkları hedefleyen başarılı tedavi yöntemleri geliştirmek için esastır. Kanser hücrelerinin değişmiş şeker metabolizmasına olan bağımlılığını bozmayı amaçlayan terapötik müdahaleler, tümör büyümesini durdurma ve hasta sonuçlarını iyileştirme konusunda büyük bir umut taşımaktadır.

Kaynakça

  • Upadhyay, M., et al., The Warburg effect: insights from the past decade. Pharmacology & therapeutics, 2013. 137(3): p. 318-330. doi.org/10.1016/j. pharmthera.2012.11.003
  • Danhier, P., et al., Cancer metabolism in space and time: beyond the Warburg effect. Biochimica et Biophysica Acta (BBA)- Bioenergetics, 2017. 1858(8): p. 556-572. doi.org/10.1016/j.bbabio.2017.02.001
  • Pascale, R.M., et al., The Warburg effect 97 years after its discovery. Cancers, 2020. 12(10): p. 2819. doi.org/10.3390/ cancers12102819
  • Afonso, J., et al., Competitive glucose metabolism as a target to boost bladder cancer immunotherapy. Nature Reviews Urology, 2020. 17(2): p. 77-106.
  • Pérez-Tomás, R. and I. Pérez-Guillén, Lactate in the tumor microenvironment: an essential molecule in cancer progression and treatment. Cancers, 2020. 12(11): p. 3244. doi.org/10.3390/cancers12113244
  • Lunt, S.Y. and M.G. Vander Heiden, Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annual review of cell and developmental biology, 2011. 27(1): p. 441-464. doi.org/10.1146/ annurev-cellbio-092910-154237
  • Wu, W. and S. Zhao, Metabolic changes in cancer: beyond the Warburg effect. Acta Biochim Biophys Sin, 2013. 45(1): p. 18- 26. doi.org/10.1093/abbs/gms104
  • Demicco, M., et al., Metabolic heterogeneity in cancer. Nature Metabolism, 2024. 6(1): p. 18-38.
  • Krstic, J., T.R. Pieber, and A. Prokesch, Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine. International Review of Cell and Molecular Biology, 2020. 354: p. 231-259. doi. org/10.1016/bs.ircmb.2020.03.001
  • Fadaka, A., et al., Biology of glucose metabolization in cancer cells. Journal of Oncological Sciences, 2017. 3(2): p. 45- 51. doi.org/10.1016/j.jons.2017.06.002
  • Vazquez, A., et al., Cancer metabolism at a glance. Journal of cell science, 2016. 129(18):p.3367-3373.doi.org/10.1242/ jcs.181016
  • Lu, J., M. Tan, and Q. Cai, The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an antimetastasis mechanism.Cancer letters, 2015. 356(2):p.156-164.doi.org/10.1016/j. canlet.2014.04.001
  • Mayes, P.A. and D.A. Bender, Glycolysis and the oxidation of pyruvate. a LANGE medical book, 2003: p. 136.
  • Carbó, R. and E. Rodríguez, Relevance of Sugar Transport across the Cell Membrane. International Journal of Molecular Sciences, 2023. 24(7): p. 6085. doi. org/10.3390/ijms24076085
  • Pavlova, N.N. and C.B. Thompson, The emerging hallmarks of cancer metabolism. Cell metabolism, 2016. 23(1): p. 27-47.
  • Adekola, K.,S.T. Rosen, and M. Shanmugam, Glucose transporters in cancer metabolism. Current opinion in oncology, 2012. 24(6):p.650.DOI: 10.1097/ CCO.0b013e328356da72
  • Vander Heiden, M.G., L.C. Cantley, and C.B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. science, 2009. 324(5930): p. 1029-1033. DOI: 10.1126/ science.1160809
  • de la Cruz-López, K.G., et al., Lactate in the regulation of tumor microenvironment and therapeutic approaches. Frontiers in oncology, 2019.9: p. 1143. doi.org/10.3389/ fonc.2019.01143
  • Choi, S.Y.C., et al., Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? The Journal of pathology, 2013. 230(4): p. 350-355. doi.org/10.1002/ path.4218
  • Diaz-Ruiz, R., M. Rigoulet, and A. Devin, The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression. Biochimica et Biophysica Acta (BBA)- Bioenergetics, 2011. 1807(6): p. 568-576. doi.org/10.1016/j.bbabio.2010.08.010
  • Chandel, N.S., Glycolysis. Cold Spring Harbor Perspectives in Biology, 2021. 13(5): p. a040535. doi: 10.1101/ cshperspect.a040535
  • Givan, C.V., Evolving concepts in plant glycolysis: two centuries of progress. Biological Reviews, 1999. 74(3): p. 277- 309. doi.org/10.1017/S0006323199005344
  • DeBerardinis, R.J., et al., Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences, 2007. 104(49): p.19345-19350.doi.org/10.1073/ pnas.0709747104
  • Wilson, D.F., Oxidative phosphorylation: regulation and role in cellular and tissue metabolism. The Journal of physiology, 2017. 595(23): p. 7023-7038. doi. org/10.1113/JP273839
  • Gupta, S., A. Roy, and B.S. Dwarakanath, Metabolic cooperation and competition in the tumor microenvironment: implications for therapy. Frontiers in oncology, 2017. 7: p. 68. doi.org/10.3389/fonc.2017.00068
  • Jiang, P., W. Du, and M. Wu, Regulation of the pentose phosphate pathway in cancer. Protein & cell, 2014. 5(8): p. 592-602. doi. org/10.1007/s13238-014-0082-8
  • Tao, Z., et al., Breast cancer: epidemiology and etiology. Cell biochemistry and biophysics, 2015. 72: p. 333-338.
  • Qadir, A.M., et al., Evaluation of Melatonin and Antioxidant Levels in the Serum of Breast Cancer Patients. BioMed Target Journal, 2024. 2(1): p. 35-42. doi. org/10.59786/bmtj.215
  • Tanoue, L.T., et al., Lung cancer screening. American journal of respiratory and critical care medicine, 2015. 191(1): p. 19-33. doi. org/10.1164/rccm.201410-1777CI
  • Tsouko, E., et al., Regulation of the pentose phosphate pathway by an androgen receptor–mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis, 2014. 3(5): p. e103-e103. doi:10.1038/oncsis.2014.18
  • Jóźwiak, P., et al., O-GlcNAcylation and metabolic reprograming in cancer. Frontiers in endocrinology, 2014. 5: p. 145. doi.org/10.3389/fendo.2014.00145
  • Kumar, M., et al., Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene, 2011. 30(7): p. 843-853.
  • Yao, S., Expression of the extended facilitative glucose transporter family (GLUT) in mouse adipose tissue. 2005, University of Liverpool.
  • Mueckler, M. and C. Makepeace, Model of the exofacial substrate-binding site and helical folding of the human Glut1 glucose transporter based on scanning mutagenesis. Biochemistry, 2009. 48(25): p. 5934-5942. doi.org/10.1021/bi900521n
  • Brown, R.S. and R.L. Wahl, Overexpression of glut-1 glucose transporter in human breast cancer an immunohistochemical study. Cancer, 1993.72(10): p.2979-2985.doi.org/10.1002/1097- 0142(19931115)72:10<2979::AIDCNCR2820721020> 3.0.CO;2-X
  • Fendt, S.-M., C. Frezza, and A. Erez, Targeting metabolic plasticity and flexibility dynamics for cancer therapy. Cancer discovery, 2020. 10(12): p. 1797- 1807. doi.org/10.1158/2159-8290.CD-20- 0844
  • Kreuzaler, P., et al., Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion. Molecular metabolism, 2020. 33: p. 83-101. doi. org/10.1016/j.molmet.2019.08.021
  • Meskers, C.J., et al., Are we still on the right path (way)?: the altered expression of the pentose phosphate pathway in solid tumors and the potential of its inhibition in combination therapy. Expert Opinion on Drug Metabolism & Toxicology, 2022. 18(1): p. 61-83. doi.org/10.1080/17425255 .2022.2049234
  • DeBerardinis, R.J. and N.S. Chandel, Fundamentals of cancer metabolism. Science advances, 2016. 2(5): p. e1600200. DOI: 10.1126/sciadv.1600200
  • Jiang, M., H. Fang, and H. Tian, Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer. Theranostics, 2025. 15(1): p. 155. doi: 10.7150/thno.103376

Metabolic Reprogramming in Early Cancer: Altered Sugar and its Role in Tumorigenesis

Yıl 2025, Cilt: 8 Sayı: 2, 117 - 127, 18.07.2025

Öz

Metabolic reprogramming is a hallmark of cancer, playing an essential role in carcinogenesis and the initial steps of cancer development. This phenomenon involves alterations in cellular metabolism, particularly in using sugars, which provide the essential energy and building blocks for tumour growth and propagation. This review focuses on the metabolic reprogramming associated with early cancer and its impact on sugar metabolism. Cancer cells exhibit enhanced glucose uptake and utilisation, commonly known as the Warburg effect, which allows for rapid Adenosine Triphosphate production and biomass synthesis. Additionally, cancer cells demonstrate increased glycolytic flux, diverting glucose metabolites towards anabolic pathways that support cell growth. Oncogenic signalling pathways, including activation of key regulators and alterations in tumour suppressor genes such as the p53 gene, drive these alterations in sugar metabolism. Renewing sugar metabolism in cancer cells provides a selective advantage, facilitating tumour survival and progression. Moreover, metabolic alterations in early cancer promote the generation of intermediates for biosynthesis, redox balance, and post-translational modifications, further contributing to tumorigenesis. Comprehending the complexities of metabolic reprogramming in early cancer is essential for formulating successful treatment methods that target metabolic vulnerabilities. Therapeutic interventions aimed at disrupting cancer cells' addiction to altered sugar metabolism hold great promise in halting tumour growth and improving patient outcomes.

Teşekkür

Thank you very much

Kaynakça

  • Upadhyay, M., et al., The Warburg effect: insights from the past decade. Pharmacology & therapeutics, 2013. 137(3): p. 318-330. doi.org/10.1016/j. pharmthera.2012.11.003
  • Danhier, P., et al., Cancer metabolism in space and time: beyond the Warburg effect. Biochimica et Biophysica Acta (BBA)- Bioenergetics, 2017. 1858(8): p. 556-572. doi.org/10.1016/j.bbabio.2017.02.001
  • Pascale, R.M., et al., The Warburg effect 97 years after its discovery. Cancers, 2020. 12(10): p. 2819. doi.org/10.3390/ cancers12102819
  • Afonso, J., et al., Competitive glucose metabolism as a target to boost bladder cancer immunotherapy. Nature Reviews Urology, 2020. 17(2): p. 77-106.
  • Pérez-Tomás, R. and I. Pérez-Guillén, Lactate in the tumor microenvironment: an essential molecule in cancer progression and treatment. Cancers, 2020. 12(11): p. 3244. doi.org/10.3390/cancers12113244
  • Lunt, S.Y. and M.G. Vander Heiden, Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annual review of cell and developmental biology, 2011. 27(1): p. 441-464. doi.org/10.1146/ annurev-cellbio-092910-154237
  • Wu, W. and S. Zhao, Metabolic changes in cancer: beyond the Warburg effect. Acta Biochim Biophys Sin, 2013. 45(1): p. 18- 26. doi.org/10.1093/abbs/gms104
  • Demicco, M., et al., Metabolic heterogeneity in cancer. Nature Metabolism, 2024. 6(1): p. 18-38.
  • Krstic, J., T.R. Pieber, and A. Prokesch, Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine. International Review of Cell and Molecular Biology, 2020. 354: p. 231-259. doi. org/10.1016/bs.ircmb.2020.03.001
  • Fadaka, A., et al., Biology of glucose metabolization in cancer cells. Journal of Oncological Sciences, 2017. 3(2): p. 45- 51. doi.org/10.1016/j.jons.2017.06.002
  • Vazquez, A., et al., Cancer metabolism at a glance. Journal of cell science, 2016. 129(18):p.3367-3373.doi.org/10.1242/ jcs.181016
  • Lu, J., M. Tan, and Q. Cai, The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an antimetastasis mechanism.Cancer letters, 2015. 356(2):p.156-164.doi.org/10.1016/j. canlet.2014.04.001
  • Mayes, P.A. and D.A. Bender, Glycolysis and the oxidation of pyruvate. a LANGE medical book, 2003: p. 136.
  • Carbó, R. and E. Rodríguez, Relevance of Sugar Transport across the Cell Membrane. International Journal of Molecular Sciences, 2023. 24(7): p. 6085. doi. org/10.3390/ijms24076085
  • Pavlova, N.N. and C.B. Thompson, The emerging hallmarks of cancer metabolism. Cell metabolism, 2016. 23(1): p. 27-47.
  • Adekola, K.,S.T. Rosen, and M. Shanmugam, Glucose transporters in cancer metabolism. Current opinion in oncology, 2012. 24(6):p.650.DOI: 10.1097/ CCO.0b013e328356da72
  • Vander Heiden, M.G., L.C. Cantley, and C.B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. science, 2009. 324(5930): p. 1029-1033. DOI: 10.1126/ science.1160809
  • de la Cruz-López, K.G., et al., Lactate in the regulation of tumor microenvironment and therapeutic approaches. Frontiers in oncology, 2019.9: p. 1143. doi.org/10.3389/ fonc.2019.01143
  • Choi, S.Y.C., et al., Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? The Journal of pathology, 2013. 230(4): p. 350-355. doi.org/10.1002/ path.4218
  • Diaz-Ruiz, R., M. Rigoulet, and A. Devin, The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression. Biochimica et Biophysica Acta (BBA)- Bioenergetics, 2011. 1807(6): p. 568-576. doi.org/10.1016/j.bbabio.2010.08.010
  • Chandel, N.S., Glycolysis. Cold Spring Harbor Perspectives in Biology, 2021. 13(5): p. a040535. doi: 10.1101/ cshperspect.a040535
  • Givan, C.V., Evolving concepts in plant glycolysis: two centuries of progress. Biological Reviews, 1999. 74(3): p. 277- 309. doi.org/10.1017/S0006323199005344
  • DeBerardinis, R.J., et al., Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences, 2007. 104(49): p.19345-19350.doi.org/10.1073/ pnas.0709747104
  • Wilson, D.F., Oxidative phosphorylation: regulation and role in cellular and tissue metabolism. The Journal of physiology, 2017. 595(23): p. 7023-7038. doi. org/10.1113/JP273839
  • Gupta, S., A. Roy, and B.S. Dwarakanath, Metabolic cooperation and competition in the tumor microenvironment: implications for therapy. Frontiers in oncology, 2017. 7: p. 68. doi.org/10.3389/fonc.2017.00068
  • Jiang, P., W. Du, and M. Wu, Regulation of the pentose phosphate pathway in cancer. Protein & cell, 2014. 5(8): p. 592-602. doi. org/10.1007/s13238-014-0082-8
  • Tao, Z., et al., Breast cancer: epidemiology and etiology. Cell biochemistry and biophysics, 2015. 72: p. 333-338.
  • Qadir, A.M., et al., Evaluation of Melatonin and Antioxidant Levels in the Serum of Breast Cancer Patients. BioMed Target Journal, 2024. 2(1): p. 35-42. doi. org/10.59786/bmtj.215
  • Tanoue, L.T., et al., Lung cancer screening. American journal of respiratory and critical care medicine, 2015. 191(1): p. 19-33. doi. org/10.1164/rccm.201410-1777CI
  • Tsouko, E., et al., Regulation of the pentose phosphate pathway by an androgen receptor–mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis, 2014. 3(5): p. e103-e103. doi:10.1038/oncsis.2014.18
  • Jóźwiak, P., et al., O-GlcNAcylation and metabolic reprograming in cancer. Frontiers in endocrinology, 2014. 5: p. 145. doi.org/10.3389/fendo.2014.00145
  • Kumar, M., et al., Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene, 2011. 30(7): p. 843-853.
  • Yao, S., Expression of the extended facilitative glucose transporter family (GLUT) in mouse adipose tissue. 2005, University of Liverpool.
  • Mueckler, M. and C. Makepeace, Model of the exofacial substrate-binding site and helical folding of the human Glut1 glucose transporter based on scanning mutagenesis. Biochemistry, 2009. 48(25): p. 5934-5942. doi.org/10.1021/bi900521n
  • Brown, R.S. and R.L. Wahl, Overexpression of glut-1 glucose transporter in human breast cancer an immunohistochemical study. Cancer, 1993.72(10): p.2979-2985.doi.org/10.1002/1097- 0142(19931115)72:10<2979::AIDCNCR2820721020> 3.0.CO;2-X
  • Fendt, S.-M., C. Frezza, and A. Erez, Targeting metabolic plasticity and flexibility dynamics for cancer therapy. Cancer discovery, 2020. 10(12): p. 1797- 1807. doi.org/10.1158/2159-8290.CD-20- 0844
  • Kreuzaler, P., et al., Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion. Molecular metabolism, 2020. 33: p. 83-101. doi. org/10.1016/j.molmet.2019.08.021
  • Meskers, C.J., et al., Are we still on the right path (way)?: the altered expression of the pentose phosphate pathway in solid tumors and the potential of its inhibition in combination therapy. Expert Opinion on Drug Metabolism & Toxicology, 2022. 18(1): p. 61-83. doi.org/10.1080/17425255 .2022.2049234
  • DeBerardinis, R.J. and N.S. Chandel, Fundamentals of cancer metabolism. Science advances, 2016. 2(5): p. e1600200. DOI: 10.1126/sciadv.1600200
  • Jiang, M., H. Fang, and H. Tian, Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer. Theranostics, 2025. 15(1): p. 155. doi: 10.7150/thno.103376
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Gıda Özellikleri, Halk Sağlığı Beslenmesi, Klinik Beslenme
Bölüm Derleme
Yazarlar

Amjad Mahmood Qadir 0000-0002-4142-6118

Abbas Salihi 0000-0002-1342-2849

Abdalla Hama 0000-0002-9722-6369

Gönderilme Tarihi 18 Mart 2025
Kabul Tarihi 25 Nisan 2025
Yayımlanma Tarihi 18 Temmuz 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 8 Sayı: 2

Kaynak Göster

APA Qadir, A. M., Salihi, A., & Hama, A. (2025). Metabolic Reprogramming in Early Cancer: Altered Sugar and its Role in Tumorigenesis. Tıp Fakültesi Klinikleri Dergisi, 8(2), 117-127.


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