Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
| العنوان: | Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells |
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| المؤلفون: | Biljana Blagojevic, Fadi Almouhanna, Ali Ghanem, Stefan Wölfl, Suzan Can |
| المصدر: | Cancer & Metabolism, Vol 9, Iss 1, Pp 1-17 (2021) Cancer & Metabolism |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | AMPK, Chemistry, Research, PKM2, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer metabolism, lcsh:RC254-282, Cell biology, Psychiatry and Mental health, Breast cancer, Anaerobic glycolysis, Phosphorylation, Glycolysis, Pyruvate kinase, TXNIP, Intracellular, Pyruvate kinase M2 |
| الوصف: | Background Aerobic glycolysis, discovered by Otto Warburg, is a hallmark of cancer metabolism even though not yet fully understood. The low activity of the cancerous pyruvate kinase isozyme (M2) is thought to play an important role by facilitating the conversion of glycolytic intermediates to other anabolic pathways to support tumors’ high proliferation rate. Methods Five breast cancer cell lines representing different molecular subtypes were used in this study where real time measurements of cellular bioenergetics and immunoblotting analysis of energy- and nutrient-sensing pathways were employed to investigate the potential effects of PKM2 allosteric activator (DASA-58) in glucose rewiring. Results In this study, we show that DASA-58 can induce pyruvate kinase activity in breast cancer cells without affecting the overall cell survival. The drug is also able to reduce TXNIP levels (an intracellular glucose sensor) probably through depletion of upstream glycolytic metabolites and independent of AMPK and ER signaling. AMPK shows an induction in phosphorylation (T172) in response to treatment an effect that can be potentiated by combining DASA-58 with other metabolic inhibitors. Conclusions Altogether, the multifaceted metabolic reprogramming induced by DASA-58 in breast cancer cells increases their susceptibility to other therapeutics suggesting the suitability of the intracellular glucose sensor TXNIP as a marker of PK activity. |
| اللغة: | English |
| تدمد: | 2049-3002 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1682c37ad2d31bb92b4527a9d31cc0ef https://doaj.org/article/9cc2a292ae774d3891c40b5511b6ff7f |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1682c37ad2d31bb92b4527a9d31cc0ef |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20493002 |
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