The pentose phosphate pathway and cancer

Patra, Krushna C.; Hay, Nissim

doi:10.1016/j.tibs.2014.06.005

Cited by 1,039 publications

(920 citation statements)

References 67 publications

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“…2). Cancer cells use multiple metabolic pathways to generate NADPH, including the pentose phosphate (Patra and Hay 2014), folate , and malic enzyme pathways (Fig. 2).…”

Section: Cancer Cells Undergo Metabolic Changes To Manage Rosmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

207

141

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Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.

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“…2). Cancer cells use multiple metabolic pathways to generate NADPH, including the pentose phosphate (Patra and Hay 2014), folate , and malic enzyme pathways (Fig. 2).…”

Section: Cancer Cells Undergo Metabolic Changes To Manage Rosmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

207

141

View full text Add to dashboard Cite

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“…The pentose phosphate pathway (PPP) is an alternative route for Glc metabolism, yielding ribose 5-phosphate (R5P) for nucleotide biosynthesis and NADPH for fatty acid biosynthesis and decomposition of peroxides (20). The choice of tracer for analysis depends on the research question as LC-MS or ion chromatography-MS can detect most of the PPP intermediates (21,22).…”

Section: Pentose Phosphate Pathwaymentioning

confidence: 99%

Exploring cancer metabolism using stable isotope-resolved metabolomics (SIRM)

Bruntz

Lane

Higashi

et al. 2017

Journal of Biological Chemistry

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Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.Metabolism is the collection of predominantly enzyme-catalyzed biochemical transformations that meet the growth and survival demands of an organism. For nearly a century, scientists have documented profound metabolic changes that occur in tumors (1, 2). One of the earliest insights into cancer metabolism came when Otto Warburg noted increased uptake and fermentation of glucose (Glc) 3 to lactate in tumors relative to surrounding tissue, even in the presence of ample oxygen (2). Clinical cancer diagnosis exploits this "Warburg effect" by measuring uptake of the Glc analogue 18 F-deoxyglucose using positron emission tomography (PET), as the metabolic demands of differentiated, non-proliferating tissues generally require far less Glc than tumors (3).Oncoproteins and tumor suppressors are well-established regulators of metabolism, and mutations or dysregulated expression can lead to the altered metabolic phenotypes observed in many cancers (4, 5). Inactivating mutations in enzymes such as fumarate hydratase (FH) or succinate dehydrogenase (SDH) induce pathophysiological accumulation of substrates that inhibit other critical enzyme functions, whereas less common gain-of-function mutations such as in isocitrate dehydrogenases (IDH) produce metabolites that directly deregulate cellular processes (6). Additionally, cancer cells frequently express fetal isoforms of metabolic enzymes that are subject to different regulatory mechanisms to provide growth advantages (7). Gaining a systematic understanding of the metabolic changes that occur during carcinogenesis can thus be exploited for therapeutic and diagnostic purposes.Stable isotope-resolved metabolomics (SIRM) is a powerful approach developed by others and by us where isotopically enriched precursors such as [ 13 C 6 ]Glc are administered to a biological system, and the ensuing metabolic transformations are determined using appropriate analytic techniques to enable robust reconstruction of metabolic pathways (8 -11). Stable isotopes are non-radioactive and in SIRM practice are identical chemically and functionally to the most abundant isotope of that element. Incorporating stable isotopes such as 2 H, 13 C, or 15 N into biological precursors has long been used to trace their metabolism in living systems (12). SIRM is thus distinct from non-tracer-based metabolomics profiling for statistical models. Here, we review SIRM applications and demonstrate h...

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“…After being converted to glucose-6-phosphate, some of the increased glucose uptake is shunted into the pentose phosphate pathway, to generate ribose and nicotinamide adenine dinucleotide phosphate (NADPH). Both ribose and NADPH are integral in the biosynthesis of nucleotides and fatty acids, which are in high demand in rapidly dividing cancer cells (42). NADPH also serves as the antioxidant substrate for the glutathione (GSH) and thioredoxin antioxidant systems, helping to reduce levels of reactive oxygen species (ROS) in the cell (Fig.…”

Section: Metabolic Heterogeneitymentioning

confidence: 99%

Intratumoral Heterogeneity: From Diversity Comes Resistance

Pribluda¹,

Cruz²,

Jackson³

2015

Clinical Cancer Research

119

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Tumors consist of a heterogeneous mixture of functionally distinct cancer cells. These functional differences can be caused by varying levels of receptor activity, differentiation, and distinct metabolic and epigenetic states. Intratumoral heterogeneity can lead to interdependence among different subpopulations of cells for sustained tumor growth. In addition, subpopulations can vary widely in their responses to therapeutic agents. As such, it is believed that intratumoral heterogeneity may underlie incomplete treatment responses, acquired and innate resistance, and disease relapse observed in the clinic in response to conventional chemotherapy and targeted agents. Clin Cancer Res; 21(13); 2916-23.Ó2015 AACR.

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The pentose phosphate pathway and cancer

Cited by 1,039 publications

References 67 publications

Cancer, Oxidative Stress, and Metastasis

Cancer, Oxidative Stress, and Metastasis

Exploring cancer metabolism using stable isotope-resolved metabolomics (SIRM)

Intratumoral Heterogeneity: From Diversity Comes Resistance

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