Warburg and Beyond: The Power of Mitochondrial Metabolism to Collaborate or Replace Fermentative Glycolysis in Cancer

Cassim, Shamir; Vučetić, Milica; Ždralević, Maša; Pouysségur, Jacques

doi:10.3390/cancers12051119

Cited by 139 publications

(114 citation statements)

References 192 publications

(269 reference statements)

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“…In a recent interesting review, Cassim and coworkers [ 205 ] report that mitochondria play a key function in tumorigenesis. To explain the role of LDH in tumor growth, these authors disrupted the LDHA and LDHB genes in the human colon adenocarcinoma and murine melanoma cells [ 206 ]. The knockout of each of these genes did not strongly reduced lactate secretion, which was instead fully suppressed in the double knockout cells (LDHA/B-DKO).…”

Section: The Warburg Effect and Tumor Therapymentioning

confidence: 99%

The Warburg Effect 97 Years after Its Discovery

Pascale

Calvisi

Simile

et al. 2020

Cancers

211

128

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The deregulation of the oxidative metabolism in cancer, as shown by the increased aerobic glycolysis and impaired oxidative phosphorylation (Warburg effect), is coordinated by genetic changes leading to the activation of oncogenes and the loss of oncosuppressor genes. The understanding of the metabolic deregulation of cancer cells is necessary to prevent and cure cancer. In this review, we illustrate and comment the principal metabolic and molecular variations of cancer cells, involved in their anomalous behavior, that include modifications of oxidative metabolism, the activation of oncogenes that promote glycolysis and a decrease of oxygen consumption in cancer cells, the genetic susceptibility to cancer, the molecular correlations involved in the metabolic deregulation in cancer, the defective cancer mitochondria, the relationships between the Warburg effect and tumor therapy, and recent studies that reevaluate the Warburg effect. Taken together, these observations indicate that the Warburg effect is an epiphenomenon of the transformation process essential for the development of malignancy.

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Section: The Warburg Effect and Tumor Therapymentioning

confidence: 99%

The Warburg Effect 97 Years after Its Discovery

Pascale

Calvisi

Simile

et al. 2020

Cancers

211

128

View full text Add to dashboard Cite

show abstract

“…16 A defining hallmark of tumor phenotypes is uncontrolled cell proliferation, while fermentative glycolysis has long been considered as one of the major metabolic pathways that allows energy production and provides intermediates for the anabolic growth of cancer cells. 17 Gemcitabine has been used as a first-line treatment alone for pancreatic cancer; however, a frequent occurrence of gemcitabine resistance has been observed. There are various molecular mechanisms that lead to chemoresistance, and in a general view, many of those have been linked to a stemness-associated survival phenotype.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate 3′-sialyllactose as a novel target for theranostics in pancreatic ductal adenocarcinoma

et al. 2020

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We previously demonstrated that the carbohydrate 3′-sialyllactose is overexpressed in cancer stem-like cells such as metastatic pancreatic and poorly differentiated gastric cancer cells, and undifferentiated human embryonic stem cells. In this study, we investigated the possibility of 3′-sialyllactose as a target for theranostics in cancers using a recombinant mouse monoclonal antibody r3B1E2 that binds to 3′-sialyllactose. Immunohistochemistry analysis confirmed an elevated expression of 3′-sialyllactose in tumors of pancreas, stomach, and testis, while no expression of 3′-sialyllactose was observed in corresponding normal controls. In addition, a stage-independent expression of 3′-sialyllactose was observed, especially in pancreatic ductal adenocarcinoma (PDAC). The level of serum 3′-sialyllactose in PDAC subjects was significantly higher than that in healthy controls, providing excellent AUC of 0.88. We next explored the therapeutic potential of r3B1E2 for PDAC in vitro. Treatment of r3B1E2 with 3′-sialyllactose-bearing human PDAC cells exhibited a complement-dependent cytotoxicity, whereas no significant activity of r3B1E2 against 3′-sialyllactose-negative cells was observed. Collectively, these findings raise the possibility of 3′-sialyllactose as a novel target for theranostics in PDAC.

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“…Instead of entering the tricarboxylic acid cycle, most of pyruvate is converted to lactate. This excess of lactate diffuses in the extracellular environment and is picked up by oxygenated cells, that revert the lactate to pyruvate and enhance their oxidative phosphorylation (Cassim et al, 2020;Parks et al, 2020). Consequently, their need for glucose decreased, and more glucose is available for the more hypoxic area of tumors (Nakajima and Van Houten, 2013).…”

Section: Tumor Metabolic Adaptationmentioning

confidence: 99%

Resistance to Anti-angiogenic Therapies: A Mechanism Depending on the Time of Exposure to the Drugs

Montemagno

Pagès

2020

Front. Cell Dev. Biol.

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Angiogenesis, the formation of new blood vessels from preexisting one, represents a critical process for oxygen and nutrient supply to proliferating cells, therefore promoting tumor growth and metastasis. The Vascular Endothelial Growth Factor (VEGF) pathway is one of the key mediators of angiogenesis in cancer. Therefore, several therapies including monoclonal antibodies or tyrosine kinase inhibitors target this axis. Although preclinical studies demonstrated strong antitumor activity, clinical studies were disappointing. Antiangiogenic drugs, used to treat metastatic patients suffering of different types of cancers, prolonged survival to different extents but are not curative. In this review, we focused on different mechanisms involved in resistance to antiangiogenic therapies from early stage resistance involving mainly tumor cells to late stages related to the adaptation of the microenvironment.

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Warburg and Beyond: The Power of Mitochondrial Metabolism to Collaborate or Replace Fermentative Glycolysis in Cancer

Cited by 139 publications

References 192 publications

The Warburg Effect 97 Years after Its Discovery

The Warburg Effect 97 Years after Its Discovery

Carbohydrate 3′-sialyllactose as a novel target for theranostics in pancreatic ductal adenocarcinoma

Resistance to Anti-angiogenic Therapies: A Mechanism Depending on the Time of Exposure to the Drugs

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