‘The Metabolism of Tumours’: 70 Years Later

Semenza, Gregg L.; Artemov, Dmitri; Bedi, Atul; Bhujwalla, Zaver M.; Chiles, Kelly A.; Feldser, David M.; Laughner, Erik; Ravi, Rajani; Simons, Jonathan W.; Taghavi, Panthea; Zhong, Hua

doi:10.1002/0470868716.ch17

Cited by 179 publications

(104 citation statements)

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“…T cells do not typically respond directly to insulin, yet comparable to insulin regulation of Glut4, CD28 provides a signal to T cell metabolism and growth that is mediated by induction of Glut1 and regulation of Glut1 trafficking. Similar to T cell activation, cancer cells also often show elevated Glut1 expression and glycolytic metabolism (45,46). Understanding the regulatory pathways underlying this metabolic phenotype may therefore provide useful insight into immunological and neoplastic diseases, as well as illustrate the critical role that nutrition may have on immune function.…”

Section: Discussionmentioning

confidence: 99%

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Jacobs

Herman

MacIver

et al. 2008

The Journal of Immunology

701

766

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T cell activation potently stimulates cellular metabolism to support the elevated energetic and biosynthetic demands of growth, proliferation, and effector function. We show that glucose uptake is limiting in T cell activation and that CD28 costimulation is required to allow maximal glucose uptake following TCR stimulation by up-regulating expression and promoting the cell surface trafficking of the glucose transporter Glut1. Regulation of T cell glucose uptake and Glut1 was critical, as low glucose prevented appropriate T cell responses. Additionally, transgenic expression of Glut1 augmented T cell activation, and led to accumulation of readily activated memory-phenotype T cells with signs of autoimmunity in aged mice. To further examine the regulation of glucose uptake, we analyzed CD28 activation of Akt, which appeared necessary for maximal glucose uptake of stimulated cells and which we have shown can promote Glut1 cell surface trafficking. Consistent with a role for Akt in Glut1 trafficking, transgenic expression of constitutively active myristoylated Akt increased glucose uptake of resting T cells, but did not alter Glut1 protein levels. Therefore, CD28 appeared to promote Akt-independent up-regulation of Glut1 and Akt-dependent Glut1 cell surface trafficking. In support of this model, coexpression of Glut1 and myristoylated Akt transgenes resulted in a synergistic increase in glucose uptake and accumulation of activated T cells in vivo that were largely independent of CD28. Induction of Glut1 protein and Akt regulation of Glut1 trafficking are therefore separable functions of CD28 costimulation that cooperate to promote glucose metabolism for T cell activation and proliferation.

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Section: Discussionmentioning

confidence: 99%

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Jacobs

Herman

MacIver

et al. 2008

The Journal of Immunology

701

766

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“…In addition to the six recognized hallmarks of cancer, aerobic glycolysis or the Warburg effect is also a robust metabolic hallmark of most tumors [10][11][12][13][14]. Although no specific gene mutation or chromosomal abnormality is common to all cancers [7,[15][16][17], nearly all cancers express aerobic glycolysis, regardless of their tissue or cellular origin.…”

Section: Introductionmentioning

confidence: 99%

Cancer as a Metabolic Disease

Seyfried¹

2012

192

291

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Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

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“…Tumor cells often have an increased glucose metabolism due to their preferential use of glycolysis for energy generation and to the overexpression of glucose transporters (GLUTs). 46 The most commonly used agent to measure increased glucose metabolism is 2-deoxy-2-[ 18 F]fluoro-D-glucose which is widely used in tumor diagnosis, staging, and monitoring therapeutic response. 47,48 The imaging is done by the use of positron emission tomography (PET).…”

Section: Probes That Image Increased Cell-metabolismmentioning

confidence: 99%

The use of fluorescent dyes and probes in surgical oncology

Velde

Veerman

Subramaniam

et al. 2010

European Journal of Surgical Oncology (EJSO)

130

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Aims and background: Improved visualization of surgical targets inside of the patient helps to improve radical resection of the tumor while sparing healthy surrounding tissue. In order to achieve an image, optical contrast must be generated by properties intrinsic to the tissue, or require the attachment of special visualization labels to the tumor. In this overview the current status of the clinical use of fluorescent dyes and probes are reviewed. Methods:In this review, all experimental and clinical studies concerning fluorescent imaging were included. In addition, in the search for the optimal fluorescent imaging modality, all characteristics of a fluorescent dye were described. Findings and Conclusions:Although the technique of imaging through fluorescence sounds promising and several animal models show efficacy, official approval of these agents for further clinical evaluation, is eagerly awaited.

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‘The Metabolism of Tumours’: 70 Years Later

Cited by 179 publications

References 0 publications

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways

Cancer as a Metabolic Disease

The use of fluorescent dyes and probes in surgical oncology

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