Lab Report
Gottlieb Scientific Report 2012 (107.82 kB)
Key Publications
Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O’Reilly M, Gottlieb E. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491: 458-62, 2012
Frezza C, Zheng L, Folger O, Rajagopalan KN, Mackenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, Ruppin E, Gottlieb E (2011). Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477(7363): 225-8, 2011
Tennant DA, Frezza C, Mackenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E.
Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene 28: 4009-21, 2009
Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E. Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol. 183: 681-96, 2008
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nadano K, Bartrons R, Gottlieb E, Vousden, KH. TIGAR, a novel regulator of glycolysis and apoptosis, is induced by p53. Cell 126: 107-120, 2006
Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Yi P, Simon MC, Thompson CB, Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7: 77-85, 2005
Recent Publications
2013
Kaplon J, Zheng L, Meissl K, Chaneton B, Selivanov VA, MacKay G, van der
Burg SH, Verdegaal EME, Cascante M, Shlomi T, Gottlieb E*, Peeper DS*. A
critical role for the mitochondrial gatekeeper pyruvate dehydrogenase
in oncogene-induced senescence. Nature, in press 2013 (*Equal
Contribution)
Zheng L, MacKenzie ED, Karim SA, Hedley A, Blyth K, Kalna G, Watson DG, Szlosarek P, Frezza C, Gottlieb E. Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer & Metabolism 1: 12, 2013
Gonzalvez F, D'Aurelio M, Boutant M, Moustapha A, Puech JP, Landes T, Arnauré L, Vial G, Talleux N, Slomianny C, Wanders RJ, Houtkooper RH, Belenger P, Møller IM, Gottlieb E, Vaz FM, Manfredi G, Petit PX. Barth syndrome: Cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin gene mutation. Biochim Biophys Acta. in press 2013
Jalmar O, François-Moutal L, García-Sáez AJ, Perry M, Granjon T,
Gonzalvez F, Gottlieb E, Ayala-Sanmartin J, Klösgen B, Schwille P, Petit
PX. Caspase-8 binding to cardiolipin in giant unilamellar vesicles
provides a functional docking platform for bid. PLoS One 8(2): e55250,
2013
Long JS, Crighton D, O’Prey J, MacKay G, Zheng L, Palmer TM, Gottlieb E,
Kevin M. Ryan KM. Extracellular adenosine sensing - a metabolic cell
death priming mechanism downstream of p53. Molecular Cell, in press 2013
Maddocks ODK, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E,
Vousden KH.
Serine starvation induces stress and p53 dependent metabolic remodeling
in cancer cells. Nature 493: 542-6, 2013
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM,
McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng
L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce
K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin
H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ,
O’Neill LAJ. Succinate is an inflammatory signal that induces IL-1β
through HIF-1α. Nature 496: 238–42, 2013
2012
Duran RV, Mackenzie ED, Boulahbel H, Frezza C, Heiserich L, Tardito S,
Bussolati O, Rocha S, Hall
MN, Gottlieb E.
HIF-independent role of prolyl hydroxylases in the cellular response to
amino acids. Oncogene doi: 10.1038/onc.2012.465, published online 22 Oct
2012
Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O’Reilly M, Gottlieb E.
Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491: 458-62, 2012
Duran RV, Oppliger W, Robitaille AM, Heiserich L, Skendaj R, Gottlieb E, Hall MN.
Glutaminolysis Activates Rag-mTORC1 Signaling. Mol Cell 47: 349-58, 2012
Chaneton B, Gottlieb E.
PGAMgnam style: A glycolytic switch controls biosynthesis. Cancer Cell 22: 565-6, 2012
Chaneton B, Gottlieb E.
Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci 37: 309-16, 2012
Schug ZT, Frezza C, Galbraith LC, Gottlieb E.
The music of lipids: how lipid composition orchestrates cellular behaviour. Acta Oncol
51: 301-10, 2012
2011
Frezza C, Zheng L, Folger O, Rajagopalan KN, Mackenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A, Kalna G, Tomlinson IP, Pollard PJ, Watson DG, Deberardinis RJ, Shlomi T, Ruppin E, Gottlieb E (2011). Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477(7363):225-8, 2011
Frezza C, Zheng L, Tennant DA, Papkovsky DB,
Hedley BA, Kalna G, Watson DG, Gottlieb E.
Metabolic profiling of hypoxic cells revealed a
catabolic signature required for cell survival. PLoS
One 2011; 6: e24411
Schug ZT, Gonzalvez F, Houtkooper RH, Vaz FM,
Gottlieb E.
BID is cleaved by caspase-8 within a native complex
on the mitochondrial membrane. Cell Death Differ
2011; 18: 538–48
Gottlieb E (2011). p53 guards the metabolic pathway less travelled. Nat Cell Biol. 13, 195-7.
Frezza C, Pollard PJ, Gottlieb E (2011). Inborn and acquired metabolic defects in cancer. J Mol Med. 89, 213-20.
Folger O, Jerby L, Frezza C, Gottlieb E, Ruppin E, Shlomi T (2011). Predicting selective drug targets in cancer through metabolic networks. Mol Syst Biol. 7, 517.
Shlomi T, Benyamini T, Gottlieb E, Sharan R, Ruppin E (2011). Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect. PLoS Comput Biol 7, e1002018.
Galluzzi L, Vitale I, Abrams JM, Alnemri ES,
Baehrecke EH, Blagosklonny MV, Dawson TM,
Dawson VL, El-Deiry WS, Fulda S, Gottlieb E,
Green DR, Hengartner MO, Kepp O, Knight RA,
Kumar S, Lipton SA, Lu X, Madeo F, Malorni W,
Mehlen P, Nunez G, Peter ME, Piacentini M,
Rubinsztein DC, Shi Y, Simon HU, Vandenabeele
P, White E, Yuan J, Zhivotovsky B, Melino G,
Kroemer G.
Molecular definitions of cell death subroutines:
recommendations of the Nomenclature Committee
on Cell Death 2012. Cell Death Differ doi:
10.1038/cdd.2011.96, published online 15 Jul 2011
2010
Tennant DA, Gottlieb E (2010). HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression. J Mol Med. 88, 839-49.
Tennant DA, Duran RV, Gottlieb E (2010). Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 10, 267-77.
2009
Tennant DA, Frezza C, Mackenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E (2009).
Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene 28, 4009-21.
Boulahbel H, Duran RV, Gottlieb E (2009). Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans. 37, 291-4.
Frezza C, Gottlieb E (2009). Mitochondria in Cancer: Not just innocent bystanders. Seminars in Cancer Biology 19, 4-11.
Gottlieb E (2009). Cancer: The fat and the furious. Nature 461, 44-5.
King A, Gottlieb E (2009). Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective. Curr Opin
Cell Biol. 21, 885-93.
Schug ZT, Gottlieb E (2009). Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta 1788, 2022-31.
Tennant DA, Duran RV, Boulahbel H, Gottlieb E (2009). Metabolic transformation in cancer. Carcinogenesis 30, 1269-80.
2008
Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E (2008). Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol. 183, 681-96.
Cancer cells must duplicate their genome, synthesise proteins and lipids, and assemble these components to form daughter cells. These activities require increased uptake of nutrients to be used as biosynthetic precursors and energy. However, rapid tumour growth surpasses the required blood supply and exposes cancer cells to conditions of metabolic stress. Therefore, cancer cells undergo many metabolic changes
that support growth and survival. 
