The Warburg Phenomenon and Other Metabolic Alterations of Cancer Cells

2010 ◽  
pp. 39-66 ◽  
Author(s):  
Gabriel D. Dakubo
Keyword(s):  
Cancer Cells ◽  
Metabolic Alterations ◽  
Warburg Phenomenon

scholarly journals Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3485
Author(s):  
Assunta Sellitto ◽  
Giovanni Pecoraro ◽  
Giorgio Giurato ◽  
Giovanni Nassa ◽  
Francesca Rizzo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Metabolic Alterations ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Additional Level

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

scholarly journals Arkaitz Carracedo: If the scientific question is good, the result will be interesting

2019 ◽  
Vol 216 (11) ◽  
pp. 2449-2450
Author(s):  
Stephanie Houston
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Oxidation ◽  
Principal Investigator ◽  
Acid Oxidation ◽  
Cooperative Research ◽  
Scientific Question ◽  
Metabolic Alterations

Arkaitz Carracedo is a principal investigator at the Association for Cooperative Research in Biosciences (CIC bioGUNE) in Spain; his laboratory focuses on signaling and metabolic alterations in cancer. Arkaitz has investigated the regulation of fatty acid oxidation in cancer cells and how these changes could be manipulated therapeutically. We chatted with Arkaitz to find out about his career in science so far.

scholarly journals Metabolic Alterations in Pancreatic Cancer Progression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Enza Vernucci ◽  
Jaime Abrego ◽  
Venugopal Gunda ◽  
Surendra K. Shukla ◽  
Aneesha Dasgupta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Precancerous Lesions ◽  
Genetically Engineered ◽  
Metabolic Reprogramming ◽  
Pancreatic Tumors ◽  
Metabolic Alterations ◽  
Genetically Engineered Mice

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions.

scholarly journals The Involvement of PPARs in the Peculiar Energetic Metabolism of Tumor Cells

2018 ◽  
Author(s):  
Andrea Antonosante ◽  
Michele d'Angelo ◽  
Vanessa Castelli ◽  
Mariano Catanesi ◽  
Dalila Iannotta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Cancer Metabolism ◽  
Cholesterol Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Energetic Metabolism ◽  
Metabolic Alterations ◽  
Long Time

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

scholarly journals Metabolic Alterations in Cancer and Their Potential as Therapeutic Targets

2017 ◽  
pp. 825-832
Author(s):  
Jamie D. Weyandt ◽  
Craig B. Thompson ◽  
Amato J. Giaccia ◽  
W. Kimryn Rathmell
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Patient Outcomes ◽  
Metabolic Changes ◽  
Tumor Proliferation ◽  
Therapeutic Targeting ◽  
Normal Cells ◽  
Metabolic Alterations ◽  
Improve Patient

Otto Warburg’s discovery in the 1920s that tumor cells took up more glucose and produced more lactate than normal cells provided the first clues that cancer cells reprogrammed their metabolism. For many years, however, it was unclear as to whether these metabolic alterations were a consequence of tumor growth or an adaptation that provided a survival advantage to these cells. In more recent years, interest in the metabolic differences in cancer cells has surged, as tumor proliferation and survival have been shown to be dependent upon these metabolic changes. In this educational review, we discuss some of the mechanisms that tumor cells use for reprogramming their metabolism to provide the energy and nutrients that they need for quick or sustained proliferation and discuss the potential for therapeutic targeting of these pathways to improve patient outcomes.

Pyruvate uptake is increased in highly invasive ovarian cancer cells under anoikis conditions for anaplerosis, mitochondrial function, and migration

2012 ◽  
Vol 303 (8) ◽  
pp. E1036-E1052 ◽  
Author(s):  
Christine A. Caneba ◽  
Nadège Bellance ◽  
Lifeng Yang ◽  
Lisa Pabst ◽  
Deepak Nagrath
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Mitochondrial Activity ◽  
Anoikis Resistance ◽  
Migration Ability ◽  
Metabolic Alterations ◽  
Less Invasive ◽  
Nutrient Demand

Anoikis resistance, or the ability for cells to live detached from the extracellular matrix, is a property of epithelial cancers. The “Warburg effect,” or the preference of cancer cells for glycolysis for their energy production even in the presence of oxygen, has been shown to be evident in various tumors. Since a cancer cell's metastatic ability depends on microenvironmental conditions (nutrients, stromal cells, and vascularization) and is highly variable for different organs, their cellular metabolic fluxes and nutrient demand may show considerable differences. Moreover, a cancer cell's metastatic ability, which is dependent on the stage of cancer, may further create metabolic alterations depending on its microenvironment. Although recent studies have aimed to elucidate cancer cell metabolism under detached conditions, the nutrient demand and metabolic activity of cancer cells under nonadherent conditions remain poorly understood. Additionally, less is known about metabolic alterations in ovarian cancer cells with varying invasive capability under anoikis conditions. We hypothesized that the metabolism of highly invasive ovarian cancer cells in detachment would differ from less invasive ovarian cancer cells and that ovarian cancer cells will have altered metabolism in detached vs. attached conditions. To assess these metabolic differences, we integrated a secretomics-based metabolic footprinting (MFP) approach with mitochondrial bioenergetics. Interestingly, MFP revealed higher pyruvate uptake and oxygen consumption in more invasive ovarian cancer cells than their less invasive counterparts. Furthermore, ATP production was higher in more invasive vs. less invasive ovarian cancer cells in detachment. We found that pyruvate has an effect on highly invasive ovarian cancer cells' migration ability. Our results are the first to demonstrate that higher mitochondrial activity is related to higher ovarian cancer invasiveness under detached conditions. Importantly, our results bring insights regarding the metabolism of cancer cells under nonadherent conditions and could lead to the development of therapies for modulating cancer cell invasiveness.

scholarly journals Coenzyme Q Depletion Reshapes MCF-7 Cells Metabolism

2020 ◽  
Vol 22 (1) ◽  
pp. 198
Author(s):  
Wenping Wang ◽  
Irene Liparulo ◽  
Nicola Rizzardi ◽  
Paola Bolignano ◽  
Natalia Calonghi ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Coenzyme Q ◽  
Glucose Consumption ◽  
Tca Cycle ◽  
Glutamine Metabolism ◽  
Metabolic Alterations ◽  
Metabolic Characteristics ◽  
Mcf 7

Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells. Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions. Results: we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls. Conclusion: This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting.

Sign in / Sign up

Export Citation Format

Share Document