scholarly journals An Anti-tumorigenic Role of the Warburg Effect at Emergence of Transformed Cells

2018 ◽  
Vol 43 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Kojiro Ishibashi ◽  
Riku Egami ◽  
Kazuki Nakai ◽  
Shunsuke Kon
Keyword(s):  
Warburg Effect ◽  
Transformed Cells ◽  
The Warburg Effect

scholarly journals MYC regulates metabolism through vesicular transfer of glycolytic kinases

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Alexia Tsakaneli ◽  
Victor Corasolla Carregari ◽  
Martina Morini ◽  
Alessandra Eva ◽  
Giuliana Cangemi ◽  
...  
Keyword(s):  
Warburg Effect ◽  
Neuroblastoma Cells ◽  
Mass Spectrometry Analysis ◽  
Target Cells ◽  
Hexokinase Ii ◽  
Childhood Malignancy ◽  
Spectrometry Analysis ◽  
Functional Consequences ◽  
The Warburg Effect

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.

scholarly journals Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6434
Author(s):  
Aldona Kasprzak
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Glucose Metabolism ◽  
Warburg Effect ◽  
Mapk Signaling ◽  
Colorectal Carcinogenesis ◽  
Insulin Like Growth Factor ◽  
Aberrant Expression ◽  
The Warburg Effect

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.

scholarly journals Extracellular citrate and metabolic adaptations of cancer cells

2021 ◽  
Author(s):  
E. Kenneth Parkinson ◽  
Jerzy Adamski ◽  
Grit Zahn ◽  
Andreas Gaumann ◽  
Fabian Flores-Borja ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Immune Cells ◽  
Warburg Effect ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
The Warburg Effect

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.

scholarly journals Evolved resistance to GAPDH inhibition results in loss of the Warburg Effect but retains a different state of glycolysis

2019 ◽  
Author(s):  
Maria V. Liberti ◽  
Annamarie E. Allen ◽  
Vijyendra Ramesh ◽  
Ziwei Dai ◽  
Katherine R. Singleton ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Acid Metabolism ◽  
Aerobic Glycolysis ◽  
Specific Inhibitor ◽  
Central Carbon Metabolism ◽  
Glycolytic Enzyme ◽  
Altered State ◽  
The Warburg Effect

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.

Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

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

scholarly journals Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect

2011 ◽  
Vol 108 (39) ◽  
pp. 16259-16264 ◽  
Author(s):  
C. Zhang ◽  
M. Lin ◽  
R. Wu ◽  
X. Wang ◽  
B. Yang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Warburg Effect ◽  
Target Gene ◽  
P53 Target Gene ◽  
The Warburg Effect

scholarly journals Role of Warburg Effect in Cardiovascular Diseases: A Potential Treatment Option

2021 ◽  
Vol 15 (1) ◽  
pp. 6-17
Author(s):  
Niken Puspa Kuspriyanti ◽  
Eko Fuji Ariyanto ◽  
Mas Rizky A. A. Syamsunarno
Keyword(s):  
Fatty Acids ◽  
Cardiovascular Diseases ◽  
Treatment Option ◽  
Warburg Effect ◽  
Energy Demand ◽  
Energy Shift ◽  
Potential Treatment ◽  
Abstract Screening ◽  
The Warburg Effect

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.

scholarly journals Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect

2017 ◽  
Vol 114 (43) ◽  
pp. 11440-11445 ◽  
Author(s):  
Smriti Singh ◽  
Sathiya Pandi Narayanan ◽  
Kajal Biswas ◽  
Amit Gupta ◽  
Neha Ahuja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
The Warburg Effect

Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to normal PKM1 isoform. This results in the reversal of the Warburg effect and the inhibition of breast cancer cell growth, which may serve as a useful approach to inhibit the growth of breast cancer cells. Importantly, our results show that in addition to PKM splicing, BORIS also regulates the alternative splicing of several genes in a DNA methylation-dependent manner. Our findings highlight the role of intragenic DNA methylation and DNA binding protein BORIS in cancer-specific splicing and its role in tumorigenesis.

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