Faculty Opinions recommendation of Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect.

Author(s):  
Hans van Beek
2011 ◽  
Vol 7 (3) ◽  
pp. e1002018 ◽  
Author(s):  
Tomer Shlomi ◽  
Tomer Benyamini ◽  
Eyal Gottlieb ◽  
Roded Sharan ◽  
Eytan Ruppin

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Alexia Tsakaneli ◽  
Victor Corasolla Carregari ◽  
Martina Morini ◽  
Alessandra Eva ◽  
Giuliana Cangemi ◽  
...  

Amplification of the proto-oncogene MYCN is a key molecular aberration in high-risk neuroblastoma and predictive of poor outcome in this childhood malignancy. We investigated the role of MYCN in regulating the protein cargo of extracellular vesicles (EVs) secreted by tumour cells that can be internalized by recipient cells with functional consequences. Using a switchable MYCN system coupled to mass spectrometry analysis, we found that MYCN regulates distinct sets of proteins in the EVs secreted by neuroblastoma cells. EVs produced by MYCN-expressing cells or isolated from neuroblastoma patients induced the Warburg effect, proliferation and c-MYC expression in target cells. Mechanistically, we linked the cancer-promoting activity of EVs to the glycolytic kinase pyruvate kinase M2 (PKM2) that was enriched in EVs secreted by MYC-expressing neuroblastoma cells. Importantly, the glycolytic enzymes PKM2 and hexokinase II were detected in the EVs circulating in the bloodstream of neuroblastoma patients, but not in those of non-cancer children. We conclude that MYC-activated cancers might spread oncogenic signals to remote body locations through EVs.


2018 ◽  
Vol 43 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Kojiro Ishibashi ◽  
Riku Egami ◽  
Kazuki Nakai ◽  
Shunsuke Kon

2021 ◽  
Vol 22 (12) ◽  
pp. 6434
Author(s):  
Aldona Kasprzak

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.


Author(s):  
E. Kenneth Parkinson ◽  
Jerzy Adamski ◽  
Grit Zahn ◽  
Andreas Gaumann ◽  
Fabian Flores-Borja ◽  
...  

Abstract It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.


2019 ◽  
Author(s):  
Maria V. Liberti ◽  
Annamarie E. Allen ◽  
Vijyendra Ramesh ◽  
Ziwei Dai ◽  
Katherine R. Singleton ◽  
...  

SUMMARYAerobic glycolysis or the Warburg Effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although ubiquitous, the biological role of the WE remains controversial and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, we evolved resistance to koningic acid (KA), a natural product shown to be a specific inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme during the WE. We find that KA-resistant cells lose the WE but conduct glycolysis and surprisingly remain dependent on glucose and central carbon metabolism. Consequentially this altered state of glycolysis leads to differential metabolic activity and requirements including emergent activities in and dependencies on fatty acid metabolism. Together, these findings reveal that, contrary to some recent reports, aerobic glycolysis is a functionally distinct entity from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.


2015 ◽  
Vol 42 (4) ◽  
pp. 841-851 ◽  
Author(s):  
Rupert Courtnay ◽  
Darleen C. Ngo ◽  
Neha Malik ◽  
Katherine Ververis ◽  
Stephanie M. Tortorella ◽  
...  

2011 ◽  
Vol 108 (39) ◽  
pp. 16259-16264 ◽  
Author(s):  
C. Zhang ◽  
M. Lin ◽  
R. Wu ◽  
X. Wang ◽  
B. Yang ◽  
...  

2021 ◽  
Vol 15 (1) ◽  
pp. 6-17
Author(s):  
Niken Puspa Kuspriyanti ◽  
Eko Fuji Ariyanto ◽  
Mas Rizky A. A. Syamsunarno

Background: Under normal conditions, the heart obtains ATP through the oxidation of fatty acids, glucose, and ketones. While fatty acids are the main source of energy in the heart, under certain conditions, the main source of energy shifts to glucose where pyruvate converts into lactate, to meet the energy demand. The Warburg effect is the energy shift from oxidative phosphorylation to glycolysis in the presence of oxygen. This effect is observed in tumors as well as in diseases, including cardiovascular diseases. If glycolysis is more dominant than glucose oxidation, the two pathways uncouple, contributing to the severity of the heart condition. Recently, several studies have documented changes in metabolism in several cardiovascular diseases; however, the specific mechanisms remain unclear. Methods: This literature review was conducted by an electronic database of Pub Med, Google Scholar, and Scopus published until 2020. Relevant papers are selected based on inclusion and exclusion criteria. Results: A total of 162 potentially relevant articles after the title and abstract screening were screened for full-text. Finally, 135 papers were included for the review article. Discussion: This review discusses the effects of alterations in glucose metabolism, particularly the Warburg effect, on cardiovascular diseases, including heart failure, atrial fibrillation, and cardiac hypertrophy. Conclusion: Reversing the Warburg effect could become a potential treatment option for cardiovascular diseases.


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