Articles

Metabolomics of oncogene-specific metabolic reprogramming during breast cancer

The complex yet interrelated connections between cancer metabolism and oncogenic driver genes are relatively unexplored but have the potential to identify novel biomarkers and drug targets with prognostic and ...

Authors: Chen Dai, Jennifer Arceo, James Arnold, Arun Sreekumar, Norman J. Dovichi, Jun Li and Laurie E. Littlepage

Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state

Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, ...

Authors: Parmanand Malvi, Balkrishna Chaube, Shivendra Vikram Singh, Naoshad Mohammad, Maleppillil Vavachan Vijayakumar, Snahlata Singh, Surbhi Chouhan and Manoj Kumar Bhat

Cancer cell metabolic plasticity allows resistance to NAMPT inhibition but invariably induces dependence on LDHA

Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD⁺ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAM...

Authors: Natthakan Thongon, Chiara Zucal, Vito Giuseppe D’Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron and Alessandro Provenzani

Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase

Folate-dependent one-carbon metabolism provides one-carbon units for several biological processes. This pathway is highly compartmentalized in eukaryotes, with the mitochondrial pathway producing formate for u...

Authors: Minhye Shin, Jessica Momb and Dean R. Appling

PKM2 is not required for colon cancer initiated by APC loss

Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been repor...

Authors: Allison N. Lau, William J. Israelsen, Jatin Roper, Mark J. Sinnamon, Larissa Georgeon, Talya L. Dayton, Alissandra L. Hillis, Omer H. Yilmaz, Dolores Di Vizio, Kenneth E. Hung and Matthew G. Vander Heiden

Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids

Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvi...

Authors: Caroline H. Johnson, Antonio F. Santidrian, Sarah E. LeBoeuf, Michael E. Kurczy, Nicholas J. W. Rattray, Zahra Rattray, Benedikt Warth, Melissa Ritland, Linh T. Hoang, Celine Loriot, Jason Higa, James E. Hansen, Brunhilde H. Felding and Gary Siuzdak

Molecular features that predict the response to antimetabolite chemotherapies

Antimetabolite chemotherapeutic agents that target cellular metabolism are widely used in the clinic and are thought to exert their anti-cancer effects mainly through non-specific cytotoxic effects. However, p...

Authors: Mahya Mehrmohamadi, Seong Ho Jeong and Jason W. Locasale

Bortezomib resistance in multiple myeloma is associated with increased serine synthesis

The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an...

Authors: Esther A. Zaal, Wei Wu, Gerrit Jansen, Sonja Zweegman, Jacqueline Cloos and Celia R. Berkers

Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities

Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique met...

Authors: Nathan J. Lanning, Joshua P. Castle, Simar J. Singh, Andre N. Leon, Elizabeth A. Tovar, Amandeep Sanghera, Jeffrey P. MacKeigan, Fabian V. Filipp and Carrie R. Graveel

HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma

A key feature of clear cell renal cell carcinoma (ccRCC) is the inactivation of the von Hippel-Lindau tumour suppressor protein (pVHL) that leads to the activation of hypoxia-inducible factor (HIF) pathway als...

Authors: Petra Miikkulainen, Heidi Högel, Krista Rantanen, Tomi Suomi, Petri Kouvonen, Laura L. Elo and Panu M. Jaakkola

The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours: evidence of a β-hydroxybutyrate paradox

Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour gro...

Authors: Loreta M. Rodrigues, Santiago Uribe-Lewis, Basetti Madhu, Davina J. Honess, Marion Stubbs and John R. Griffiths

The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity

Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents ...

Authors: Renaud Vatrinet, Giulia Leone, Monica De Luise, Giulia Girolimetti, Michele Vidone, Giuseppe Gasparre and Anna Maria Porcelli

Mitochondrial mutations and metabolic adaptation in pancreatic cancer

Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic str...

Authors: Rae-Anne Hardie, Ellen van Dam, Mark Cowley, Ting-Li Han, Seher Balaban, Marina Pajic, Mark Pinese, Mary Iconomou, Robert F. Shearer, Jessie McKenna, David Miller, Nicola Waddell, John V. Pearson, Sean M. Grimmond, Leonid Sazanov, Andrew V. Biankin…

Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration

Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to sup...

Authors: Seher Balaban, Robert F. Shearer, Lisa S. Lee, Michelle van Geldermalsen, Mark Schreuder, Harrison C. Shtein, Rose Cairns, Kristen C. Thomas, Daniel J. Fazakerley, Thomas Grewal, Jeff Holst, Darren N. Saunders and Andrew J. Hoy

The role of tumor metabolism as a driver of prostate cancer progression and lethal disease: results from a nested case-control study

Understanding the biologic mechanisms underlying the development of lethal prostate cancer is critical for improved therapeutic and prevention strategies. In this study we explored the role of tumor metabolism...

Authors: Rachel S. Kelly, Jennifer A. Sinnott, Jennifer R. Rider, Ericka M. Ebot, Travis Gerke, Michaela Bowden, Andreas Pettersson, Massimo Loda, Howard D. Sesso, Philip W. Kantoff, Neil E. Martin, Edward L. Giovannucci, Svitlana Tyekucheva, Matthew Vander Heiden and Lorelei A. Mucci

Weight control interventions improve therapeutic efficacy of dacarbazine in melanoma by reversing obesity-induced drug resistance

Obesity-related cellular, metabolic, and molecular alterations have been shown to increase cancer risk and tumor progression and are associated with poorer therapeutic outcome in cancer patients. However, the ...

Authors: Parmanand Malvi, Balkrishna Chaube, Shivendra Vikram Singh, Naoshad Mohammad, Vimal Pandey, Maleppillil Vavachan Vijayakumar, Revathy Meenatheril Radhakrishnan, Muralidharan Vanuopadath, Sudarslal Sadasivan Nair, Bipin Gopalakrishnan Nair and Manoj Kumar Bhat

Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy with dismal prognosis. Metastatic spread and therapeutic resistance, the main causes of PDAC-related mortalities, are both partially underlined by...

Authors: Menghan Liu, Lake-Ee Quek, Ghazal Sultani and Nigel Turner

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