Groupe Emérite Jacques POUYSSÉGUR



Présentation

Dr Jacques POUYSSÉGUR, DRCE CNRS Emeritus


Research Group


  "Tumour Hypoxia &

     Cancer Metabolism"

                      

                                 

POUYSSEGUR Jacques, DRCE CNRS Emeritus, Group Leader 

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Tel : +33 (0)4 92 03 12 22

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CV Jacques POUYSSÉGUR 2016 

 

Research Team :


BUSCA Roser, CR1 CNRS

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LENORMAND Philippe, CR1 INSERM

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MAZURE Nathalie, DR2 CNRS

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ONESTO Cercina, MCU UNS

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SADAGHIANLOO Nirvana, PhD student

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ZDRALEVIC Masa, CDD CNRS

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Oct 2016


Group photo December  2015

 

 



Research Interest :


Over the last 35 years, J. Pouyssegur’s group has combined genetics and molecular biology to study the mechanisms of action of growth factors and has characterized the major signalling pathways controlling cell proliferation. This team has made a substantial contribution to the areas of glycolytic metabolism, intracellular pH regulation, the molecular structure of the Na/H exchanger (first to clone the human isoform) and shown that intracellular pH and MAP kinase (ERKs) signalling are critical for cell cycle entry.


During the last 15 years the group has turned its interest to another essential growth mechanism: how do cells control their nutrient supply. This key process has led them to investigate mechanisms of hypoxia signaling, angiogenesis, nutritional stress and aberrant metabolism in tumours.  


Current Interest :



Pouyssegur’s group pursues the analysis, at a fundamental level, of the physiological role for key targets induced by nutritional stress and hypoxia in tumours. The focus is on tumour aberrant glucose metabolism (Warburg effect), glycolysis, mitophagy/autophagy driven by HIF, with a special interest in translational research applied to aggressive human cancers (brain, colon, lung, breast & pancreas). Numerous anticancer targets are in the process of being validated by this team using gene disruption (ZFN, CRISPR/Cas9) in preclinical mouse models (carbonic anhydrases CA9, CA12, bicarbonate transporters NBCs, MonoCarboxylate Transporters MCT1, MCT4, their chaperone CD147/Basigin and amino acid transporters LAT1/CD98, xCT/CD98, ASBC2…). These targets all share a common participation to the ‘Darwinian’ tumour selection and progression within the hypoxic, acidic and nutrient-deprived tumour microenvironment.


Publications Dr Jacques POUYSSÉGUR, DRCE CNRS Emeritus



2016

L Counillon, Y Bouret, I Marchiq, J Pouysségur

Na+/H+ antiporter (NHE1) and lactate/H+ symporters (MCTs) in pH homeostasis and cancer metabolism.

Biochim Biophys Acta, 2016, sous presse.


2015


 

Granja S, Marchiq I, Le Floch R, Moura CS, Baltazar F, Pouyssegur J

Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.  

Oncotarget, (2015) 6(9):6708-21.


Marchiq I, Le Floch R, Roux D, Simon MP, Pouyssegur, J

Genetic Disruption of Lactate/H+ Symporters (MCTs) and their Subunit CD147/BASIGIN Sensitizes Glycolytic Tumor Cells to Phenformin. 

Cancer Research, (2015) 75:171-80.


Giuliano S, Cormerais Y, Dufies M, Grépin R, Colosetti P, Belaid A, Parola J, Martin A, Lacas-Gervais S, Mazure NM, Benhida R, Auberger P, Mograbi B, Pagès G

Resistance to sunitinib in renal clear cell carcinoma results from sequestration in lysosomes and inhibition of the autophagic flux.

Autophagy, 2015 Oct 3;11(10):1891-904.


Parks, S, Pouysségur, J

The Na+/HCO3- co-transporter SLC4A4 plays a role in growth and migration of colon and breast cancer cells.

Journal of Cellular Physiology, (2015) 230 (8), 1954-1963.


Yufune S, Satoh Y, Takamatsu I, Ohta H, Kobayashi Y, Takaenoki Y, Pagès G, Pouysségur J, Endo S, Kazama T

Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic Phenotypes as an Adult in Mice.

Science Rep., (2015) 20(5):10252.


Wehenkel M, Corr M, Edwards B, Calabrese C, Pagès G, Pouyssegur J, Vogel P, McGargil MA

Dysregulation of ERK signaling in CD4-expressing cells induces osteochondromas (IRC8P. 441)

The Journal of Immunology, (2015) 194 (1 Supplement), 129.5-129.5


Pelletier J, Roux D, Viollet B, Mazure N, Pouysségur J

AMP Kinase is dispensable for maintaining ATP levels and for survival following inhibition of glycolysis, but promotes tumour engraftment of ras-transformed fibroblasts.

Oncotarget, (2015) 20;6(14):11833-47.


Brahimi-Horn MC, Lacas-Gervais S, Adaixo R, Ilc K, Rouleau M, Notte A, Dieu M, Michiels C, Voeltzel T, Maguer-Satta V, Pelletier J, Ilie M, Hofman P, Manoury B, Schmidt A, Hiller S, Pouysségur J, Mazure N

Local mitochondrial-endolysosomal microfusion cleaves voltage-dependent anion channel 1 to promote survival in hypoxia.

Mol Cell Biol., (2015) 35(9):1491-505.


Brahimi-Horn CM, Giuliano S, Saland E, Lacas-Gervais S, Sheiko T, Pelletier J, Bourget I, Bost F, Féral C, Boulter E, Tauc M, Ivan M, Garmy-Susini B, Popa A, Mari B, Sarry JE, William J, Craigen WJ, Pouysségur J, Mazure N

Knockout of Vdac1 activates HIF through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation.

Cancer & Metabolism, (2015) 26;3:8.


Marchiq I, Albrengues J, Granja S, Gaggioli C, Pouysségur J, Simon MP

Knock out of the BASIGIN/CD147 chaperone of Lactate/H+ symporters disproves its pro-tumour action via Extracellular Matrix Metalloproteases (MMPs) induction.

Oncotarget, (2015) 6(28):24636-48.


Compan V, Pierredon S, Vanderperre B, Krznar P, Marchiq I, Zamboni N, Pouyssegur J, Martinou JC

Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor:

Investigation of the Warburg Effect.

Mol Cell., (2015) 59(3):491-501


Marchiq I, Pouysségur J

Hypoxia, Cancer Metabolism and the Therapeutic Benefit of Targeting Lactate/H+ symporters.

Journal of Molecular Medicine (2015) Jun 24.


Buscà R, Christen R, Lovern M, Clifford AM, Yue JX, Goss GG, Pouysségur J, Lenormand P

ERK1 and ERK2 present functional redundancy in tetrapods despite higher evolution rate of ERK1

BMC Evol Biol., (2015) 3;15:179.



2014


Granja S, Marchiq I, Baltazar F, Pouysségur J.

Gene disruption using zinc finger nuclease technology.

Methods Mol Biol., 2014;1165:253-60. 


Doyen J, Trastour C, Ettore F, Peyrottes I, Toussant N, Gal J, Ilc K, Roux D, Parks SK, Ferrero JM, Pouysségur J.

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome.

Biochem Biophys Res Commun., 2014, Aug 15;451(1):54-61. 


Simonnet H, Vigneron A, Pousségur J.

Conventional techniques to monitor mitochondrial oxygen consumption.

Methods Enzymol., 2014, 542, 151-161.


Pettersen OE .. Chiche J, Mazure N, Marchiq I, Parks S, Pouysségur J, ...

Targeting tumour hypoxia to prevent cancer metastasis. From Biology, Biosensing and Technology to Drug Development : the METOXIA Consortium.

J Enzyme Inhib Med Chem., 2014, 1-33.


HoWangYin KY, Loinard C, Bakker W, Guérin CL, Vilar J, D'Audigier C, Mauge L, Bruneval P, Emmerich J, Lévy BL, Pouysségur J, Smadja DM, Silvestre JS

HIF-prolyl hydroxylase 2 inhibition enhances the efficiency of mesenchymal stem cell-based therapies for the treatment of critical limb ischemia.

Stem Cells, 2014, 32(1):231-243.



2013


Parks S, Chiche J, Pouysségur, J., 
Disrupting proton dynamics and energy metabolism for cancer therapy.
Nature Rev. Cancer (2013) 3(9):611-23.
.
Lutz NW, Le Fur Y, Chiche J, Pouysségur J, Cozzone PJ.
Quantitative in-vivo characterization of intracellular and extracellular pH profiles in heterogeneous tumors: a novel method enabling multiparametric pH analysis.
Cancer Res (2013) 73 :4616-28
.
Chiche J, Ricci JE, Pouysségur J. 

Tumor hypoxia and metabolism - Towards novel anticancer approaches.
Ann Endocrinol (2013) 74(2):111-4.

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Grosso S, Doyen J, Parks SK, Bertero T, Paye A, Cardinaud B, Gounon P, Lacas-Gervais S, Noël A, Pouysségur J, Barbry P, Mazure NM, Mari B. 
MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines.
Cell Death Dis (2013) Mar 14;4:e544.

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Ilie M, Hofman V, Zangari J, Chiche J, Mouroux J, Mazure NM, Pouysségur J, Brest P, Hofman P.
Response of CAIX and CAXII to in vitro re-oxygenation and clinical significance of the combined expression in NSCLC patients.
Lung Cancer (2013) Oct;82(1):16-23. 

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Doyen J, Parks SK, Marcié S, Pouysségur J, Chiche J.
Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis.
Front Oncol., (2013) Jan 7;2:199.

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Parks SK, Mazure NM, Counillon L, Pouysségur J.
Hypoxia promotes tumor cell survival in acidic conditions by preserving ATP levels.
J Cell Physiol (2013) 228(9):1854-62.

Pelletier J, Bellot G, Pousségur J, Mazure NM
Biochemical titration of glycogen in vitro.
J Vis Exp., 2013, 24, 81.


2012


Bertero T, Grosso S, Robbe-Sermesant K, Lebrigand K, Hénaoui IS, Puisségur MP,

Fourre S, Zaragosi LE, Mazure NM, Ponzio G, Cardinaud B, Barbry P, Rezzonico R, Mari B.
"Seed-Milarity" confers to hsa-miR-210 and hsa-miR-147b similar functional activity.
PLoS One (2012) ;7(9):e44919;

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Klionsky DJ, et al. (Mazure NM)

Guidelines for the use and interpretation of assays for monitoring autophagy.
Autophagy (2012) Apr;8(4):445-544.

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Pelletier J, Bellot G, Gounon P, Lacas-Gervais S, Pouysségur J, Mazure NM.

Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival.
Front Oncol (2012) Feb;28; 2:18.

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Mammar H, Kerrou K, Nataf V, Pontvert D, Clemenceau S, Lot G, George B, Polivka M, Mokhtari K,

Ferrand R, Feuvret L, Habrand JL, Pouysségur J, Mazure N, Talbot JN.
Positron emission tomography/computed tomography imaging of residual skull base chordoma before radiotherapy using fluoromisonidazole and fluorodeoxyglucose: potential consequences for dose painting.
Int J Radiat Oncol Biol Phys (2012) Nov 1;84(3):681-7.

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Brahimi-Horn MC, Ben-Hail D, Ilie M, Gounon P, Rouleau M, Hofman V, Doyen J, Mari B,

Shoshan-Barmatz V, Hofman P, Pouysségur J, Mazure NM.
Expression of a truncated active form of VDAC1 in lung cancer associates with hypoxic cell survival

and correlates with progression to chemotherapy resistance.
Cancer Res (2012) Apr 15;72(8):2140-50.

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Pelletier J, Dayan F, Durivault J, Ilc K, Pécou E, Pouysségur J, Mazure NM.
The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression

of the p53-p21 axis.
Oncogene (2012) Jun 14;31(24):2989-3001.

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Ladroue C, Hoogewijs D, Gad S, Carcenac R, Storti F, Barrois M, Gimenez-Roqueplo AP, Leporrier M, Casadevall N, Hermine O, Kiladjian JJ, Baruchel A, Fakhoury F, Bressac-de Paillerets B, Feunteun J, Mazure N, Pouysségur J, Wenger RH, Richard S, Gardie B.
Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia.
Haematologica (2012) Jan;97(1):9-14.


Bensellam M, Duvillie B, Rybachuk G, Laybutt DR, Magnan C, Guiot Y, Pouyssegur J, Jonas JC

Glucose-induced O(2) consumption activates hypoxia inducible factors 1 and 2 in rat insulin-secreting pancreatic beta-cells.

PLoS One 7, 2012, e29807.


Chang CF, D'Souza WN, Ch'en IL, Pagès G, Pouyssegur J, Hedrick SM

Polar opposites: erk direction of CD4 T cell subsets.

J Immunol., 2012, 189, 721-731.


Chiche J, Le Fur Y, Vilmen C, Frassineti F, Daniel L, Halestra, AP, Cozzone PJ, Pouyssegur J, Lutz, N.W.

In vivo pH in metabolic-defective Ras-transformed fibroblast tumors: key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pH.

Int J Cancer, 2012, 130, 1511-1520.


Garcia J, Sandi MJ, Cordelier P, Binetruy B, Pouyssegur J, Iovann, JL, Tournaire R. 

Tie1 deficiency induces endothelial-mesenchymal transition.

EMBO Rep., 2012, 13, 431-439.


Goplen N, Karim Z, Guo L, Zhuang Y, Huang H, Gorsk, MM, Gelfand E, Pages G, Pouyssegur J, Alam R.

ERK1 is important for Th2 differentiation and development of experimental asthma.

FASEB J., 2012, 26, 1934-1945.


Otsubo Y, Satoh Y, Kodama M, Araki Y, Satomoto M, Sakamoto E, Pages G, Pouyssegur J, Endo S, Kazama T.

Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system.

Pain, 2012.


Saulnier N, Guihard S, Holy X, Decembre E, Jurdic P, Clay D, Feuillet V, Pages G, Pouyssegur J, Porteu F, et al.

ERK1 regulates the hematopoietic stem cell niches.

PLoS One 7, 2012, e30788.