In this special collection we present a selection of recent papers published in Nature and Nature Reviews Cancer that highlight the burgeoning interest in cancer metabolism.

That cancers display an altered cellular metabolism was first recognized almost a century ago, notably in Otto Warburg's description of a switch in glucose metabolism from oxidative phosphorylation to glycolysis — the Warburg effect. However, as described in the Review by Tak W. Mak and colleagues, only recently have links been established between the oncogenic pathways that drive tumorigenesis and the mechanistic basis of tumour cell metabolism. A picture is now emerging showing that cancer-related genes, such as MYC (Liu, L. et al) and isocitrate dehydrogenase 1 (Sasaki, M. et al), have substantial effects on cancer cell metabolism.

The complexities surrounding cancer metabolism are nicely summed up in the News & Views article by Robert Svensson and Reuben Shaw, which discusses AMP kinase (AMPK). This kinase is a central sensor of cellular metabolism that can both promote and suppress cancer progression. The reasons why this and other proteins associated with cancer development and metabolism can show such different effects are unclear, but they might reflect our previous inability to study cellular metabolism in its entirety, relying instead on isolated snapshots of a complex and interconnected network. Approaches that address the wider aspects of cancer metabolism have enabled Claudio Scuoppo and colleagues to show that genes involved in the polyamine–hypusine axis suppress lymphoma development, and Richard Possemato and colleagues to show that certain breast cancers are dependent on serine because of overexpression of phosphoglycerate dehydrogenase.

Tumour metabolism is also influenced by systemic metabolic status. Bruce Spiegelman and colleagues discuss potential mechanisms through which obesity contributes to cancer development.

The Human Metabolome Database currently lists some 8,500 metabolites; but numbers are expected to rise and eventually to exceed the number of human genes. Despite this complexity, a better understanding of metabolic processes will hopefully pave the way to new therapeutic interventions.

All content for this Web collection has been chosen by the collection editors and certain papers have been made freely available for 6 months thanks to support from Teva Phamaceuticals.

Barbara Marte, Senior Editor, Nature
Nicola McCarthy, Chief Editor, Nature Reviews Cancer
Sarah Seton-Rogers, Senior Editor, Nature Reviews Cancer


Original Research papers

A tumour suppressor network relying on the polyamine–hypusine axis FREE

Claudio Scuoppo, Cornelius Miething, Lisa Lindqvist, José Reyes, Cristian Ruse, Iris Appelmann, Seungtai Yoon, Alexander Krasnitz, Julie Teruya-Feldstein, Darryl Pappin, Jerry Pelletier & Scott W. Lowe

doi:10.1038/nature11126

Nature 487, 244-248 (2012)

AMD1 and eIF5A are identified as two genes involved in the polyamine–hypusine pathway, a new tumour suppressor network regulating apoptosis.

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics FREE

Masato Sasaki, Christiane B. Knobbe, Joshua C. Munger, Evan F. Lind, Dirk Brenner, Anne Brüstle, Isaac S. Harris, Roxanne Holmes, Andrew Wakeham, Jillian Haight, Annick You-Ten, Wanda Y. Li, Stefanie Schalm, Shinsan M. Su, Carl Virtanen, Guido Reifenberger, Pamela S. Ohashi, Dwayne L. Barber, Maria E. Figueroa, Ari Melnick, Juan-Carlos Zúñiga-Pflücker & Tak W. Mak

doi:10.1038/nature11323

Nature 488, 656-659 (2012)

Mutations in isocitrate dehydrogenases IDH1 and IDH2 are common in human gliomas and acute myeloid leukaemias; here, mice that carry the IDH1(R132H) mutation are described, in a new model that should help in investigating the links between mutant IDH1 and leukaemia.

AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress

Sang-Min Jeon, Navdeep S. Chandel & Nissim Hay

doi:10.1038/nature11066

Nature 485, 661-665 (2012)

A mechanism is suggested that helps tumour cells survive energy stress conditions during early stages of tumorigenesis.

Deregulated MYC expression induces dependence upon AMPK-related kinase 5 FREE

Lidan Liu, Jannes Ulbrich, Judith Müller, Torsten Wüstefeld, Lukas Aeberhard, Theresia R. Kress, Nathiya Muthalagu, Lukas Rycak, Ramona Rudalska, Roland Moll, Stefan Kempa, Lars Zender, Martin Eilers & Daniel J. Murphy

doi:10.1038/nature10927

Nature, 483, 608-612 (2012)

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation

Peppi Koivunen, Sungwoo Lee, Christopher G. Duncan, Giselle Lopez, Gang Lu, Shakti Ramkissoon, Julie A. Losman, Päivi Joensuu, Ulrich Bergmann, Stefan Gross, Jeremy Travins, Samuel Weiss, Ryan Looper, Keith L. Ligon, Roel G. W. Verhaak, Hai Yan & William G. Kaelin

doi:10.1038/nature10898

Nature, 483, 484-488 (2012)

IDH mutation impairs histone demethylation and results in a block to cell differentiation

Chao Lu, Patrick S. Ward, Gurpreet S. Kapoor, Dan Rohle, Sevin Turcan, Omar Abdel-Wahab, Christopher R. Edwards, Raya Khanin, Maria E. Figueroa, Ari Melnick, Kathryn E. Wellen, Donald M. O’Rourke, Shelley L. Berger, Timothy A. Chan, Ross L. Levine, Ingo K. Mellinghoff & Craig B. Thompson

doi:10.1038/nature10860

Nature, 483, 474�478 (2012)

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

Sevin Turcan, Daniel Rohle, Anuj Goenka, Logan A. Walsh, Fang Fang, Emrullah Yilmaz, Carl Campos, Armida W. M. Fabius, Chao Lu, Patrick S. Ward, Craig B. Thompson, Andrew Kaufman, Olga Guryanova, Ross Levine, Adriana Heguy, Agnes Viale, Luc G. T. Morris, Jason T. Huse, Ingo K. Mellinghoff & Timothy A. Chan

doi:10.1038/nature10866

Nature, 483, 479�483 (2012)

Reductive carboxylation supports growth in tumour cells with defective mitochondria

Andrew R. Mullen, William W. Wheaton, Eunsook S. Jin, Pei-Hsuan Chen, Lucas B. Sullivan, Tzuling Cheng, Youfeng Yang, W. Marston Linehan, Navdeep S. Chandel & Ralph J. DeBerardinis

doi:10.1038/nature10642

Nature 481, 385-388 (2012)

Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia

Christian M. Metallo, Paulo A. Gameiro, Eric L. Bell, Katherine R. Mattaini, Juanjuan Yang, Karsten Hiller, Christopher M. Jewell, Zachary R. Johnson, Darrell J. Irvine, Leonard Guarente, Joanne K. Kelleher, Matthew G. Vander Heiden, Othon Iliopoulos & Gregory Stephanopoulos

doi:10.1038/nature10602

Nature 481, 380-384 (2012)

Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation

Weiwei Yang, Yan Xia, Haitao Ji, Yanhua Zheng, Ji Liang, Wenhua Huang, Xiang Gao, Kenneth Aldape & Zhimin Lu

doi:10.1038/nature10598

Nature 478, 118-122 (2011)

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor FREE

Christiane A. Opitz, Ulrike M. Litzenburger, Felix Sahm, Martina Ott, Isabel Tritschler, Saskia Trump, Theresa Schumacher, Leonie Jestaedt, Dieter Schrenk, Michael Weller, Manfred Jugold, Gilles J. Guillemin, Christine L. Miller, Christian Lutz, Bernhard Radlwimmer, Irina Lehmann, Andreas von Deimling, Wolfgang Wick & Michael Platten

doi:10.1038/nature10491

Nature 478, 197-203 (2011)

Human metabolic individuality in biomedical and pharmaceutical research

Karsten Suhre, So-Youn Shin, Ann-Kristin Petersen, Robert P. Mohney, David Meredith, Brigitte Wägele, Elisabeth Altmaier, CARDIoGRAM, Panos Deloukas, Jeanette Erdmann, Elin Grundberg, Christopher J. Hammond, Martin Hrabé de Angelis, Gabi Kastenmüller, Anna Köttgen, Florian Kronenberg, Massimo Mangino, Christa Meisinger, Thomas Meitinger, Hans-Werner Mewes, Michael V. Milburn, Cornelia Prehn, Johannes Raffler, Janina S. Ried, Werner Römisch-Margl, Nilesh J. Samani, Kerrin S. Small, H. -Erich Wichmann, Guangju Zhai, Thomas Illig, Tim D. Spector, Jerzy Adamski, Nicole Soranzo & Christian Gieger

doi:10.1038/nature10354

Nature 477, 54-60 (2011)

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Christian Frezza, Liang Zheng, Ori Folger, Kartik N. Rajagopalan, Elaine D. MacKenzie, Livnat Jerby, Massimo Micaroni, Barbara Chaneton, Julie Adam, Ann Hedley, Gabriela Kalna, Ian P. M. Tomlinson, Patrick J. Pollard, Dave G. Watson, Ralph J. Deberardinis, Tomer Shlomi, Eytan Ruppin & Eyal Gottlieb

doi:10.1038/nature10363

Nature 477, 225-228 (2011)

Functional genomics reveal that the serine synthesis pathway is essential in breast cancer FREE

Richard Possemato, Kevin M. Marks, Yoav D. Shaul, Michael E. Pacold, Dohoon Kim, Kıvanç Birsoy, Shalini Sethumadhavan, Hin-Koon Woo, Hyun G. Jang, Abhishek K. Jha, Walter W. Chen, Francesca G. Barrett, Nicolas Stransky, Zhi-Yang Tsun, Glenn S. Cowley, Jordi Barretina, Nada Y. Kalaany, Peggy P. Hsu, Kathleen Ottina, Albert M. Chan, Bingbing Yuan, Levi A. Garraway, David E. Root, Mari Mino-Kenudson, Elena F. Brachtel, Edward M. Driggers & David M. Sabatini

doi:10.1038/nature10350

Nature 476, 346-350 (2011)

Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells

Andrea Facciabene, Xiaohui Peng, Ian S. Hagemann, Klara Balint, Andrea Barchetti, Li-Ping Wang, Phyllis A. Gimotty, C. Blake Gilks, Priti Lal, Lin Zhang & George Coukos

doi:10.1038/nature10169

Nature 475, 226-230 (2011)

Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis

Gina M. DeNicola, Florian A. Karreth, Timothy J. Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, Kenneth H. Yu, Charles J. Yeo, Eric S. Calhoun, Francesca Scrimieri, Jordan M. Winter, Ralph H. Hruban, Christine Iacobuzio-Donahue, Scott E. Kern, Ian A. Blair & David A. Tuveson

doi:10.1038/nature10189

Nature 475, 106-109 (2011)

Structure of mammalian AMPK and its regulation by ADP

Bing Xiao, Matthew J. Sanders, Elizabeth Underwood, Richard Heath, Faith V. Mayer, David Carmena, Chun Jing, Philip A. Walker, John F. Eccleston, Lesley F. Haire, Peter Saiu, Steven A. Howell, Rein Aasland, Stephen R. Martin, David Carling & Steven J. Gamblin

doi:10.1038/nature09932

Nature 472, 230-233 (2011)

Telomere dysfunction induces metabolic and mitochondrial compromise

Ergün Sahin, Simona Colla, Marc Liesa, Javid Moslehi, Florian L. Müller, Mira Guo, Marcus Cooper, Darrell Kotton, Attila J. Fabian, Carl Walkey, Richard S. Maser, Giovanni Tonon, Friedrich Foerster, Robert Xiong, Y. Alan Wang, Sachet A. Shukla, Mariela Jaskelioff, Eric S. Martin, Timothy P. Heffernan, Alexei Protopopov, Elena Ivanova, John E. Mahoney, Maria Kost-Alimova, Samuel R. Perry, Roderick Bronson, Ronglih Liao, Richard Mulligan, Orian S. Shirihai, Lynda Chin & Ronald A. DePinho

doi:10.1038/nature09787

Nature 470, 359-365 (2011)

Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells

Daisuke Nakada, Thomas L. Saunders & Sean J. Morrison

doi:10.1038/nature09571

Nature 468, 653-658 (2010)

Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells

Boyi Gan, Jian Hu, Shan Jiang, Yingchun Liu, Ergün Sahin, Li Zhuang, Eliot Fletcher-Sananikone, Simona Colla, Y. Alan Wang, Lynda Chin & Ronald A. DePinho

doi:10.1038/nature09595

Nature 468, 701-704 (2010)

The Lkb1 metabolic sensor maintains haematopoietic stem cell survival

Sushma Gurumurthy, Stephanie Z. Xie, Brinda Alagesan, Judith Kim, Rushdia Z. Yusuf, Borja Saez, Alexandros Tzatsos, Fatih Ozsolak, Patrice Milos, Francesco Ferrari, Peter J. Park, Orian S. Shirihai, David T. Scadden & Nabeel Bardeesy

doi:10.1038/nature09572

Nature 468, 659-663 (2010)

Heteroplasmic mitochondrial DNA mutations in normal and tumour cells

Yiping He, Jian Wu, Devin C. Dressman, Christine Iacobuzio-Donahue, Sanford D. Markowitz, Victor E. Velculescu, Luis A. Diaz Jr, Kenneth W. Kinzler, Bert Vogelstein & Nickolas Papadopoulos

doi:10.1038/nature08802

Nature 464, 610-614 (2010)

HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer

Charles J. David, Mo Chen, Marcela Assanah, Peter Canoll & James L. Manley

doi:10.1038/nature08697

Nature 463, 364-368 (2010)

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

Lenny Dang, David W. White, Stefan Gross, Bryson D. Bennett, Mark A. Bittinger, Edward M. Driggers, Valeria R. Fantin, Hyun Gyung Jang, Shengfang Jin, Marie C. Keenan, Kevin M. Marks, Robert M. Prins, Patrick S. Ward, Katharine E. Yen, Linda M. Liau, Joshua D. Rabinowitz, Lewis C. Cantley, Craig B. Thompson, Matthew G. Vander Heiden & Shinsan M. Su

doi:10.1038/nature08617

Nature 462, 739-744 (2009)

Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment

Zachary T. Schafer, Alexandra R. Grassian, Loling Song, Zhenyang Jiang, Zachary Gerhart-Hines, Hanna Y. Irie, Sizhen Gao, Pere Puigserver & Joan S. Brugge

doi:10.1038/nature08268

Nature 462, 109-113 (2009)

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaeman Byun, Gilbert S. Omenn, Debashis Ghosh, Subramaniam Pennathur, Danny C. Alexander, Alvin Berger, Jeffrey R. Shuster, John T. Wei, Sooryanarayana Varambally, Christopher Beecher & Arul M. Chinnaiyan

doi:10.1038/nature07762

Nature 457, 910-914 (2009)

Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate

Ferdia A. Gallagher, Mikko I. Kettunen, Sam E. Day, De-En Hu, Jan Henrik Ardenkjær-Larsen, René in ‘t Zandt, Pernille R. Jensen, Magnus Karlsson, Klaes Golman, Mathilde H. Lerche & Kevin M. Brindle

doi:10.1038/nature07017

Nature 453, 940-943 (2008)

The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth

Heather R. Christofk, Matthew G. Vander Heiden, Marian H. Harris, Arvind Ramanathan, Robert E. Gerszten, Ru Wei, Mark D. Fleming, Stuart L. Schreiber & Lewis C. Cantley

doi:10.1038/nature06734

Nature 452, 230-233 (2008)

Pyruvate kinase M2 is a phosphotyrosine-binding protein

Heather R. Christofk, Matthew G. Vander Heiden, Ning Wu, John M. Asara & Lewis C. Cantley

doi:10.1038/nature06667

Nature 452, 181-186 (2008)

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Reviews

Mitochondria and cancer

Douglas C. Wallace

doi:10.1038/nrc3365

Nature Reviews Cancer 12, 685-698 (2012)

What have mitochondria ever done for us? This Review discusses why alterations in cellular processes that require mitochondria are essential for tumorigenesis.

Article series: Epigenetics and genetics

The role of mutations in epigenetic regulators in myeloid malignancies

Alan H. Shih, Omar Abdel-Wahab, Jay P. Patel & Ross L. Levine

doi:10.1038/nrc3343

Nature Reviews Cancer 12, 599-612 (2012)

Alterations to epigenetic regulators are a recently characterized class of oncogenic changes in myeloid malignancies. This Review discusses what these alterations mean for leukaemogenesis.

Aiding and abetting roles of NOX oxidases in cellular transformation

Karen Block & Yves Gorin

doi:10.1038/nrc3339

Nature Reviews Cancer 12, 627-637 (2012)

NADPH oxidases of the NOX family are reactive oxygen species-generating enzymes that regulate redox-sensitive signalling pathways. In this Review, the authors discuss primary targets and redox-linked signalling systems that are influenced by NOX-derived ROS and the biological role that NOX oxidases might have in the aetiology of cancer.

The insulin and insulin-like growth factor receptor family in neoplasia: an update

Michael Pollak

doi:10.1038/nrc3215

Nature Reviews Cancer 12, 159-169 (2012)

This Review reflects on the recent disappointing initial results from Phase III trials of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, and discusses the next steps in targeting insulin and IGFI signalling in cancer therapy.

The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention

Jeffrey M. Peters, Yatrik M. Shah & Frank J. Gonzalez

doi:10.1038/nrc3214

Nature Reviews Cancer 12, 181-195 (2012)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. This Review discusses the roles of PPARs in cancer and focuses on PPARβ/δ and the controversies yet to be resolved.

HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression

Brian Keith, Randall S. Johnson & M. Celeste Simon

doi:10.1038/nrc3183

Nature Reviews Cancer 12, 9-22 (2012)

The α-subunits that form the oxygen-sensitive component of the hypoxia-inducible factor (HIF) transcription factor have unique and overlapping roles in mediating cellular responses to hypoxia. Surprisingly, they can also have opposing roles, and the differences between HIF1α and HIF2α are discussed in this Review.

Choline metabolism in malignant transformation

Kristine Glunde, Zaver M. Bhujwalla & Sabrina M. Ronen

doi:10.1038/nrc3162

Nature Reviews Cancer 11, 835-848 (2011)

Choline metabolism is commonly deregulated in cancer, leading to increased levels of choline metabolites. This Review discusses the deregulation of choline metabolism in cancer, its reciprocal interaction with oncogenic signalling and the possible clinical applications in diagnostics and therapy.

Targeting hypoxia in cancer therapy

William R. Wilson & Michael P. Hay

doi:10.1038/nrc3064

Nature Reviews Cancer 11, 393-410 (2011)

Hypoxia is common in developing and advanced tumours and could therefore provide a means for drug selectivity. As discussed in this Review, this can be achieved either by using prodrugs that are activated in hypoxic regions, or by directly targeting hypoxia-induced signalling pathways that confer survival to tumour cells.

Otto Warburg's contributions to current concepts of cancer metabolism

Willem H. Koppenol, Patricia L. Bounds & Chi V. Dang

doi:10.1038/nrc3038

Nature Reviews Cancer 11, 325-337 (2011)

Otto Warburg has contributed important data and hypotheses to the fields of cancer research and metabolism, but what did he actually find and what conclusions did he draw? This Review looks at the life and research of Otto Warburg and places his work in the context of our current understanding of metabolism and hypoxia in cancer.

Regulation of cancer cell metabolism FREE

Rob A. Cairns, Isaac S. Harris & Tak W. Mak

doi:10.1038/nrc2981

Nature Reviews Cancer 11, 85-95 (2011)

Fundamental differences in the regulation of central metabolic pathways exist between tumours and normal tissue. This Review discusses how the Warburg effect is still applicable to our view of cancer metabolism and new advances in understanding beyond this hypothesis, including regulating anapleurosis and the redox balance.

Activity-based protein profiling for biochemical pathway discovery in cancer

Daniel K. Nomura, Melissa M. Dix & Benjamin F. Cravatt

doi:10.1038/nrc2901

Nature Reviews Cancer 10, 630-638 (2010)

This Review focuses on activity-based protein profiling, which enables the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When ABPP is integrated with other large-scale profiling methods, it can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and indicate new strategies for treatment.

Targeting metabolic transformation for cancer therapy

Daniel A. Tennant, Raúl V. Durán & Eyal Gottlieb

doi:10.1038/nrc2817

Nature Reviews Cancer 10, 267-277 (2010)

This Review discusses the progress made with developing drugs that specifically target the altered metabolic pathways of tumours and suggests additional targets that might also be beneficial.

Linking functional decline of telomeres, mitochondria and stem cells during ageing

Ergün Sahin & Ronald A. DePinho

doi:10.1038/nature08982

Nature 464, 520-528 (2010)

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Perspective

NRF2 and cancer: the good, the bad and the importance of context

Michael B. Sporn & Karen T. Liby

doi:10.1038/nrc3278

Nature Reviews Cancer 12, 564-571 (2012)

NFE2-related factor 2 (NRF2) has apparently contradictory roles in cancer. Activation of NRF2 contributes to the chemopreventive effects of various clinically used drugs against various diseases including cancer. However, NRF2 activity can also accelerate tumorigenesis in mouse models, thus highlighting a potential danger of NRF2 activation. This Opinion article discusses how these opposing roles might be reconciled.

Molecular mechanisms of cancer development in obesity FREE

Melin J. Khandekar, Paul Cohen & Bruce M. Spiegelman

doi:10.1038/nrc3174

Nature Reviews Cancer 11, 886-895 (2011)

Obesity is increasing in the developed world, and epidemiological studies indicate that this is accompanied by an increased risk of cancer. This Opinion article discusses the possible mechanisms by which obesity might promote tumorigenesis.

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News and Views

Cancer metabolism: Tumour friend or foe FREE

Robert U. Svensson & Reuben J. Shaw

doi:10.1038/485590a

Nature 485, 590-591 (2012)

Cancer: Sacrifice for survival

Nana-Maria Grüning & Markus Ralser

doi:10.1038/480190a

Nature 480, 190-191 (2011)

Cancer: Why tumours eat tryptophan

George C. Prendergast

doi:10.1038/478192a

Nature 478, 192-194 (2011)

Cancer: When antioxidants are bad

Rushika M. Perera & Nabeel Bardeesy

doi:10.1038/475043a

Nature 475, 43-44 (2011)

Genomics: Drugs, diabetes and cancer

Morris J. Birnbaum & Reuben J. Shaw

doi:10.1038/470338a

Nature 470, 338-339 (2011)

Q&A: Cancer: Clues from cell metabolism

William G. Kaelin, Jr & Craig B. Thompson

doi:10.1038/465562a

Nature 465, 562-564 (2010)

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Research Highlights

Tumour suppressors: At the hypusine of the crime

Darren J. Burgess

doi:10.1038/nrc3325

Nature Reviews Cancer 12, 509 (2012)

An in vivo short hairpin RNA screen identifies tumour suppressor genes in commonly deleted regions in lymphoma.

Metabolism: Unravelling metabolic dependencies

Darren J. Burgess

doi:10.1038/nrc3273

Nature Reviews Cancer 12, 321 (2012)

A new study identifies a metabolic dependency in prostate cancer cells.

Metabolism: Unmasking an oncometabolite

Nicola McCarthy

doi:10.1038/nrc3248

Nature Reviews Cancer 12, 229 (2012)

Mutant IDH genes that produce 2-hydroxyglutarate can influence cell transformation through effects on DNA and histone methylation and hypoxia inducible factors.

Cancer: Blocking tumour sugar metabolism

doi:10.1038/483512b

Nature 12, 512 (2012)

Genetics: IDH mosaicism in enchondromatosis syndromes

Gemma K. Alderton

doi:10.1038/nrc3194

Nature Reviews Cancer 12, 6-7 (2012)

Two papers in Nature Genetics show that the isocitrate dehydrogenases IDH1 and IDH2 are mutated in two subtypes of the cancer-prone enchondromatosis syndrome.

Kidney tumours: 'NRF said

Nicola McCarthy

doi:10.1038/nrc3175

Nature Reviews Cancer 11, 833 (2011)

Two papers have identified a new pathway through which the loss of the tumour suppressor fumarate hydratase might promote tumour development.

Metabolism: Letting glucose take hold

Gemma K. Alderton

doi:10.1038/nrc3159

Nature Reviews Cancer 11, 756 (2011)

Daley and colleagues show that LIN28-mediated suppression of let-7 microRNAs activates the insulin–PI3K–mTOR pathway to regulate glucose metabolism, connecting type 2 diabetes and cancer.

Metabolism: Catabolic effects

Sarah Seton-Rogers

doi:10.1038/nrc3161

Nature Reviews Cancer 11, 757 (2011)

A recent Nature paper identifies a catabolite of tryptophan as an endogenous ligand of aryl hydrocarbon receptor and links this pathway to tumorigenesis and suppression of antitumour immunity.

Metabolism: Haem is where the heart is

Nicola McCarthy

doi:10.1038/nrc3145

Nature Reviews Cancer 11, 692-693 (2011)

This Nature paper shows that inhibition of haem oxygenase 1 is synthetic lethal in kidney cells lacking the tumour suppressor fumarate hydratase.

Metabolism: Flexible flux

Sarah Seton-Rogers

doi:10.1038/nrc3128

Nature Reviews Cancer 11, 621 (2011)

Using unbiased functional genomics and metabolomics methods, two groups have demonstrated the importance of the serine synthesis pathway for tumorigenesis.

Systems biology: Lethal weaknesses

Nicola McCarthy

doi:10.1038/nrc3109

Nature Reviews Cancer 11, 538-539 (2011)

A new genomic-scale computer model of the cancer metabolome indicates synthetic lethal interactions.

Cancer metabolism: Feed it forward

Sarah Seton-Rogers

doi:10.1038/nrc3094

Nature Reviews Cancer 11, 461 (2011)

Semenza and colleagues identify a positive feedback loop between the pyruvate kinase PKM2 and HIF1 that may explain how PKM2 can promote metabolic reprogramming of cancer cells.

Hypoxia: HIF switch

Sarah Seton-Rogers

doi:10.1038/nrc3074

Nature Reviews Cancer 11, 391 (2011)

The switch from HIF1α-dependent to HIF2α-dependent responses may be partly mediated through the ubiquitin ligase HAF, leading to increased tumour initiation and progression.

Metabolism: The mitochondria that wag the dog

Teresa Villanueva

doi:10.1038/nrc3026

Nature Reviews Cancer 11, 155 (2011)

Canine tumours steal mitochondria from their hosts.

Metabolism: Choose your carbon source

Darren J. Burgess

doi:10.1038/nrc3009

Nature Reviews Cancer 11, 80-81 (2011)

A new study identifies a regulatory mechanism controlling carbon source uptake.

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