Articles

Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer

There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct...

Authors: Stephanie Sprowl-Tanio, Amber N. Habowski, Kira T. Pate, Miriam M. McQuade, Kehui Wang, Robert A. Edwards, Felix Grun, Yung Lyou and Marian L. Waterman

Starving cancer from the outside and inside: separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors

Calorie restriction (CR) prevents obesity and exerts anticancer effects in many preclinical models. CR is also increasingly being used in cancer patients as a sensitizing strategy prior to chemotherapy regimen...

Authors: Laura M. Lashinger, Ciara H. O’Flanagan, Sarah M. Dunlap, Audrey J. Rasmussen, Shannon Sweeney, Jessie Yangxiang Guo, Alessia Lodi, Stefano Tiziani, Eileen White and Stephen D. Hursting

A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis

Acetyl-CoA is a key metabolic intermediate with roles in the production of energy and biomass, as well as in metabolic regulation. It was recently found that acetate is crucial for maintaining acetyl-CoA produ...

Authors: Sergey Tumanov, Vinay Bulusu, Eyal Gottlieb and Jurre J. Kamphorst

Metabolic requirements for cancer cell proliferation

The study of cancer metabolism has been largely dedicated to exploring the hypothesis that oncogenic transformation rewires cellular metabolism to sustain elevated rates of growth and division. Intense examina...

Authors: Mark A. Keibler, Thomas M. Wasylenko, Joanne K. Kelleher, Othon Iliopoulos, Matthew G. Vander Heiden and Gregory Stephanopoulos

Malonate as a ROS product is associated with pyruvate carboxylase activity in acute myeloid leukaemia cells

The role of anaplerotic nutrient entry into the Krebs cycle via pyruvate carboxylase has been the subject of increased scrutiny and in particular whether this is dysregulated in cancer. Here, we use a tracer-b...

Authors: Michelle A. C. Reed, Christian Ludwig, Christopher M. Bunce, Farhat L. Khanim and Ulrich L. Günther

Novel drugs that target the metabolic reprogramming in renal cell cancer

Molecular profiling studies of tumor tissue from patients with clear cell renal cell cancer (ccRCC) have revealed extensive metabolic reprogramming in this disease. Associations were found between metabolic re...

Authors: Johannes C. van der Mijn, David J. Panka, Andrew K. Geissler, Henk. M. Verheul and James W. Mier

Fast exchange fluxes around the pyruvate node: a leaky cell model to explain the gain and loss of unlabelled and labelled metabolites in a tracer experiment

Glucose and glutamine are the two dominant metabolic substrates in cancer cells. In ¹³C tracer experiments, however, it is necessary to account for all significant input substrates, as some natural (unlabelled) s...

Authors: Lake-Ee Quek, Menghan Liu, Sanket Joshi and Nigel Turner

Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes

The heterogeneous biology of breast cancer leads to high diversity in prognosis and response to treatment, even for patients with similar clinical diagnosis, histology, and stage of disease. Identifying mechan...

Authors: Tonje H. Haukaas, Leslie R. Euceda, Guro F. Giskeødegård, Santosh Lamichhane, Marit Krohn, Sandra Jernström, Miriam R. Aure, Ole C. Lingjærde, Ellen Schlichting, Øystein Garred, Eldri U. Due, Gordon B. Mills, Kristine K. Sahlberg, Anne-Lise Børresen-Dale and Tone F. Bathen

Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool

Colorectal cancers (CRC) are associated with perturbations in cellular amino acids, nucleotides, pentose-phosphate pathway carbohydrates, and glycolytic, gluconeogenic, and tricarboxylic acid intermediates. A ...

Authors: Dustin G. Brown, Sangeeta Rao, Tiffany L. Weir, Joanne O’Malia, Marlon Bazan, Regina J. Brown and Elizabeth P. Ryan

Molecular characterization of Gleason patterns 3 and 4 prostate cancer using reverse Warburg effect-associated genes

Gleason scores (GS) 3+3 and 3+4 prostate cancers (PCa) differ greatly in their clinical courses, with Gleason pattern (GP) 4 representing a major independent risk factor for cancer progression. However, Gleaso...

Authors: Ilinca Georgescu, Robert J. Gooding, R. Christopher Doiron, Andrew Day, Shamini Selvarajah, Chris Davidson, David M. Berman and Paul C. Park

Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells

The majority of cancer cells have a unique metabolic requirement for methionine that is not observed in normal, non-tumorigenic cells. This phenotype is described as “methionine dependence” or “methionine stre...

Authors: Stacey L. Borrego, Johannes Fahrmann, Rupsa Datta, Chiara Stringari, Dmitry Grapov, Michael Zeller, Yumay Chen, Ping Wang, Pierre Baldi, Enrico Gratton, Oliver Fiehn and Peter Kaiser

Bridging the gap between non-targeted stable isotope labeling and metabolic flux analysis

Metabolism gained increasing interest for the understanding of diseases and to pinpoint therapeutic intervention points. However, classical metabolomics techniques only provide a very static view on metabolism...

Authors: Daniel Weindl, Thekla Cordes, Nadia Battello, Sean C. Sapcariu, Xiangyi Dong, Andre Wegner and Karsten Hiller

Pre-diagnosis blood glucose and prognosis in women with breast cancer

The effect of moderately elevated blood glucose levels among non-diabetic subjects on cancer prognosis is not well described. The goal of this study was to examine the association of elevated random blood gluc...

Authors: Behjatolah Monzavi-Karbassi, Rhonda Gentry, Varinder Kaur, Eric R. Siegel, Fariba Jousheghany, Srikanth Medarametla, Barbara J. Fuhrman, A. Mazin Safar, Laura F. Hutchins and Thomas Kieber-Emmons

Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments

Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzym...

Authors: Barrie Peck, Zachary T. Schug, Qifeng Zhang, Beatrice Dankworth, Dylan T. Jones, Elizabeth Smethurst, Rachana Patel, Susan Mason, Ming Jiang, Rebecca Saunders, Michael Howell, Richard Mitter, Bradley Spencer-Dene, Gordon Stamp, Lynn McGarry, Daniel James…

Profiling cancer metabolism at the ‘omic’ level: a last resort or the next frontier?

Authors: Susan J. Gelman and Gary J. Patti

Warburg effect(s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism

Virtually everyone working in cancer research is familiar with the “Warburg effect”, i.e., anaerobic glycolysis in the presence of oxygen in tumor cells. However, few people nowadays are aware of what lead Ott...

Authors: Angela M. Otto

Integration of omics: more than the sum of its parts

Genome scale data on biological systems has increasingly become available by sequencing of DNA and RNA, and by mass spectrometric quantification of proteins and metabolites. The cellular components from which ...

Authors: Joerg Martin Buescher and Edward M Driggers

The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells

Hypoxia and inflammation have been identified as hallmarks of cancer. A majority of hepatocellular carcinomas are preceded by hepatitis B- or C-related chronic infections suggesting that liver cancer developme...

Authors: Nadia Battello, Andreas David Zimmer, Carole Goebel, Xiangyi Dong, Iris Behrmann, Claude Haan, Karsten Hiller and Andre Wegner

Metabolism and microenvironment in cancer plasticity

Major contributions of the 2nd annual meeting of the International Society of Cancer Metabolism, held in Venice, September 16–19, 2015, are here described and discussed. Among these, the impact of cancer metab...

Authors: Nicola Baldini, Pierre Sonveaux, Angelo De Milito, Claudiu T. Supuran, Angela M. Otto, Christian M. Stock, Stine F. Pedersen, Rosy Favicchio and Sofia Avnet

Mathematical models of cancer metabolism

Metabolism is essential for life, and its alteration is implicated in multiple human diseases. The transformation from a normal to a cancerous cell requires metabolic changes to fuel the high metabolic demands...

Authors: Elke Katrin Markert and Alexei Vazquez

Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells

Two-hydroxyglutarate (2HG) is present at low concentrations in healthy mammalian cells as both an L and D enantiomer. Both the L and D enantiomers have been implicated in regulating cellular physiology by mech...

Authors: Susan J. Gelman, Nathaniel G. Mahieu, Kevin Cho, Elizabeth M. Llufrio, Timothy A. Wencewicz and Gary J. Patti

Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth

Numerous studies have demonstrated that functional mitochondria are required for tumorigenesis, suggesting that mitochondrial oxidative phosphorylation (OXPHOS) might be a potential target for cancer therapy. ...

Authors: Laura Schöckel, Andrea Glasauer, Farhan Basit, Katharina Bitschar, Hoa Truong, Gerrit Erdmann, Carolyn Algire, Andrea Hägebarth, Peter HGM Willems, Charlotte Kopitz, Werner JH Koopman and Mélanie Héroult

Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone

Pancreatic ductal adenocarcinomas (PDA) activate a glutamine-dependent pathway of cytosolic nicotinamide adenine dinucleotide phosphate (NADPH) production to maintain redox homeostasis and support proliferatio...

Authors: Gaurab Chakrabarti, Zachary R. Moore, Xiuquan Luo, Mariya Ilcheva, Aktar Ali, Mahesh Padanad, Yunyun Zhou, Yang Xie, Sandeep Burma, Pier P. Scaglioni, Lewis C. Cantley, Ralph J. DeBerardinis, Alec C. Kimmelman, Costas A. Lyssiotis and David A. Boothman

The rate of glycolysis quantitatively mediates specific histone acetylation sites

Glucose metabolism links metabolic status to protein acetylation. However, it remains poorly understood to what extent do features of glucose metabolism contribute to protein acetylation and whether the proces...

Authors: Ahmad A. Cluntun, He Huang, Lunzhi Dai, Xiaojing Liu, Yingming Zhao and Jason W. Locasale

¹³C-labeled biochemical probes for the study of cancer metabolism with dynamic nuclear polarization-enhanced magnetic resonance imaging

In recent years, advances in metabolic imaging have become dependable tools for the diagnosis and treatment assessment in cancer. Dynamic nuclear polarization (DNP) has recently emerged as a promising technolo...

Authors: Lucia Salamanca-Cardona and Kayvan R. Keshari

Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation

Mitochondria are more than just the powerhouse of cells; they dictate if a cell dies or survives. Mitochondria are dynamic organelles that constantly undergo fusion and fission in response to environmental con...

Authors: M. Christiane Brahimi-Horn, Sandy Giuliano, Estelle Saland, Sandra Lacas-Gervais, Tatiana Sheiko, Joffrey Pelletier, Isabelle Bourget, Frédéric Bost, Chloé Féral, Etienne Boulter, Michel Tauc, Mircea Ivan, Barbara Garmy-Susini, Alexandra Popa, Bernard Mari, Jean-Emmanuel Sarry…

Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells

Pyruvate dehydrogenase (PDH) occupies a central node of intermediary metabolism, converting pyruvate to acetyl-CoA, thus committing carbon derived from glucose to an aerobic fate rather than an anaerobic one. ...

Authors: Kartik N. Rajagopalan, Robert A. Egnatchik, Maria A. Calvaruso, Ajla T. Wasti, Mahesh S. Padanad, Lindsey K. Boroughs, Bookyung Ko, Christopher T. Hensley, Melih Acar, Zeping Hu, Lei Jiang, Juan M. Pascual, Pier Paolo Scaglioni and Ralph J. DeBerardinis

Quantification of folate metabolism using transient metabolic flux analysis

Systematic quantitative methodologies are needed to understand the heterogeneity of cell metabolism across cell types in normal physiology, disease, and treatment. Metabolic flux analysis (MFA) can be used to ...

Authors: Philip M Tedeschi, Nadine Johnson-Farley, Hongxia Lin, Laura M Shelton, Takushi Ooga, Gillian Mackay, Niels Van Den Broek, Joseph R Bertino and Alexei Vazquez

An epitope tag alters phosphoglycerate dehydrogenase structure and impairs ability to support cell proliferation

The gene encoding the serine biosynthesis pathway enzyme PHGDH is located in a region of focal genomic copy number gain in human cancers. Cells with PHGDH amplification are dependent on enzyme expression for prol...

Authors: Katherine R Mattaini, Edward J Brignole, Mitali Kini, Shawn M Davidson, Brian P Fiske, Catherine L Drennan and Matthew G Vander Heiden

Mitophagy and cancer

Mitophagy is a selective form of macro-autophagy in which mitochondria are selectively targeted for degradation in autophagolysosomes. Mitophagy can have the beneficial effect of eliminating old and/or damaged...

Authors: Aparajita H Chourasia, Michelle L Boland and Kay F Macleod

Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature

Based on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for tre...

Authors: Kenneth Schwartz, Howard T Chang, Michele Nikolai, Joseph Pernicone, Sherman Rhee, Karl Olson, Peter C Kurniali, Norman G Hord and Mary Noel

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302

Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clin...

Authors: Jonathan W Wojtkowiak, Heather C Cornnell, Shingo Matsumoto, Keita Saito, Yoichi Takakusagi, Prasanta Dutta, Munju Kim, Xiaomeng Zhang, Rafael Leos, Kate M Bailey, Gary Martinez, Mark C Lloyd, Craig Weber, James B Mitchell, Ronald M Lynch, Amanda F Baker…

Mitochondria as biosynthetic factories for cancer proliferation

Unchecked growth and proliferation is a hallmark of cancer, and numerous oncogenic mutations reprogram cellular metabolism to fuel these processes. As a central metabolic organelle, mitochondria execute critic...

Authors: Christopher S Ahn and Christian M Metallo

Erratum to: The 2014 Beatson international cancer conference: powering the cancer machine

No abstract

Authors: Jurre J Kamphorst and Daniel J Murphy

Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism

Succinate dehydrogenase (SDH) is a mitochondrial metabolic enzyme complex involved in both the electron transport chain and the citric acid cycle. SDH mutations resulting in enzymatic dysfunction have been fou...

Authors: Paul-Joseph P Aspuria, Sophia Y Lunt, Leif Väremo, Laurent Vergnes, Maricel Gozo, Jessica A Beach, Brenda Salumbides, Karen Reue, W Ruprecht Wiedemeyer, Jens Nielsen, Beth Y Karlan and Sandra Orsulic

Acetate metabolism in cancer cells

No abstract

Authors: Aaron M Hosios and Matthew G Vander Heiden

Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate

Cell growth requires fatty acids for membrane synthesis. Fatty acids are assembled from 2-carbon units in the form of acetyl-CoA (AcCoA). In nutrient and oxygen replete conditions, acetyl-CoA is predominantly ...

Authors: Jurre J Kamphorst, Michelle K Chung, Jing Fan and Joshua D Rabinowitz

The 2014 Beatson International Cancer Conference: Powering the Cancer Machine

Here, we present a report of the 2014 annual Beatson International Cancer Conference, Glasgow, July 6–9, 2014. The theme was “Powering the Cancer Machine”, focusing on oncogenic signals that regulate metabolic re...

Authors: Jurre J Kamphorst and Daniel J Murphy

Mitochondrial reactive oxygen species and cancer

Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity. While initial studies focused on the damaging effects of reactive oxygen species, a recent para...

Authors: Lucas B Sullivan and Navdeep S Chandel

Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

Authors: Debarshi Roy, Susmita Mondal, Chen Wang, Xiaoping He, Ashwani Khurana, Shailendra Giri, Robert Hoffmann, Deok-Beom Jung, Sung H Kim, Eduardo N Chini, Juliana Camacho Periera, Clifford D Folmes, Andrea Mariani, Sean C Dowdy, Jamie N Bakkum-Gamez, Shaun M Riska…

Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells

Accumulating preclinical and clinical evidence implicates epithelial-mesenchymal transition (EMT) in acquired resistance to anticancer drugs; however, mechanisms by which the mesenchymal state determines drug ...

Authors: Yuting Sun, Anneleen Daemen, Georgia Hatzivassiliou, David Arnott, Catherine Wilson, Guanglei Zhuang, Min Gao, Peter Liu, Aaron Boudreau, Leisa Johnson and Jeff Settleman

SIRT3 and SIRT4 are mitochondrial tumor suppressor proteins that connect mitochondrial metabolism and carcinogenesis

It is a well-established scientific observation that mammalian cells contain fidelity proteins that appear to protect against and adapt to various forms of endogenous and exogenous cellular conditions. Loss of...

Authors: Yueming Zhu, Yufan Yan, Daniel R Principe, Xianghui Zou, Athanassios Vassilopoulos and David Gius

Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy?

In order to solve a jigsaw puzzle, one must first have the complete picture to logically connect the pieces. However, in cancer biology, we are still gaining an understanding of all the signaling pathways that...

Authors: Rana Elkholi, Thibaud T Renault, Madhavika N Serasinghe and Jerry E Chipuk

Erratum to: Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

Authors: Surendra K Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I Pipinos, Robert Powers, Fang Yu and Pankaj K Singh

Endothelial cell metabolism: parallels and divergences with cancer cell metabolism

The stromal vasculature in tumors is a vital conduit of nutrients and oxygen for cancer cells. To date, the vast majority of studies have focused on unraveling the genetic basis of vessel sprouting (also terme...

Authors: Dries Verdegem, Stijn Moens, Peter Stapor and Peter Carmeliet

Q&A: targeting autophagy in cancer—a new therapeutic?

Macroautophagy (autophagy hereafter) captures and degrades intracellular proteins and organelles in lysosomes as a quality control mechanism and recycles their components to sustain survival in starvation. Cel...

Authors: Eileen White

Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known...

Authors: Surendra K Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I Pipinos, Robert Powers, Fang Yu and Pankaj K Singh

Metformin directly acts on mitochondria to alter cellular bioenergetics

Metformin is widely used in the treatment of diabetes, and there is interest in ‘repurposing’ the drug for cancer prevention or treatment. However, the mechanism underlying the metabolic effects of metformin r...

Authors: Sylvia Andrzejewski, Simon-Pierre Gravel, Michael Pollak and Julie St-Pierre

Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

Loss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogeni...

Authors: Debarshi Roy, Susmita Mondal, Chen Wang, Xiaoping He, Ashwani Khurana, Shailendra Giri, Robert Hoffmann, Deok-Beom Jung, Sung H Kim, Eduardo N Chini, Juliana Camacho Periera, Clifford D Folmes, Andrea Mariani, Sean C Dowdy, Jamie N Bakkum-Gamez, Shaun M Riska…

GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer

Alterations in glucose metabolism and epithelial-mesenchymal transition (EMT) constitute two important characteristics of carcinoma progression toward invasive cancer. Despite an extensive characterization of ...

Authors: Mark Masin, Jessica Vazquez, Simona Rossi, Svenja Groeneveld, Natasha Samson, Petra C Schwalie, Bart Deplancke, Laura E Frawley, Jérôme Gouttenoire, Darius Moradpour, Trudy G Oliver and Etienne Meylan