Thèmes de recherche développés
- Signalisation hypoxique et Stress nutritionnel des cancers
- Les symporters H+/Lactate et le transporteur d’acides aminés (LAT1)
- Validation de nouvelles cibles anticancer
Over the years, Pouyssegur’s group has combined genetics and molecular biology to study the mechanisms of action of growth factors and has characterized the major signaling pathways controlling cell proliferation. His team has made a substantial contribution to the areas of cell surface glycoproteins, metabolism, intracellular pH regulation, identification of human Na/H exchangers and establish that intracellular pH and MAP kinase (ERKs) signaling 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 him to investigate mechanisms of hypoxia signaling, angiogenesis, nutritional stress and aberrant metabolism in tumours.
Currently Pouyssegur’s group pursues, at a fundamental level, the physiological role for key targets induced by nutritional stress and hypoxia in tumors. The focus is on tumor aberrant glucose metabolism (Warburg effect), glycolysis, autophagy, nutrient import driven by HIF, with a special interest in translational research. Numerous anticancer targets disrupted by ZFN & CRISPR/Cas9 are in the process of being validated in preclinical mouse models, by this team (carbonic anhydrases CA9, CA12, CA2, bicarbonate transporters NBCs, MonoCarboxylate Transporters MCT1, MCT4, their chaperone CD147/Basigin and amino acid transporters LAT1/CD98, xCT, ASCT2…). These targets all share a common participation to the ‘Darwinian’ tumour selection and progression within the hypoxic, acidic and nutrient deprived tumour microenvironment.
Metrics : Web of Science citations : 42000, h-factor : 117, Google Scholar : h-factor 126
AKT1 restricts the invasive capacity of head and neck carcinoma cells harboring a constitutively active PI3 kinase activity
Brolih S, Parks S, Vial V, Durivault J, Mostosi L, Pouyssegur J, Pagès G, Picco V
BMC Cancer 18(1): 249.
Double genetic disruption of lactate dehydrogenase A and B is required to ablate the ‘Warburg effect’ restricting tumor growth to oxidative metabolism
Zdralevic M, Brand A, Di lanni L, Dettmer K, Reinders J, Singer K, Peter K, Schnell A, Bruss C, Decking S-M, Koehl G, Felipe-Abrio B, Durivault J, Bayer P, Evangelista M, O'Brien T, Oefner P J, Renner K, Pouyssegur J, Kreutz M
J Biol Chem 293(41): 15947–15961
Dynamin inhibitors block activation of mTORC1 by amino acids independently of dynamin
Persaud A, Cormerais Y, Pouyssegur J, Rotin D
J Cell Sci 131(1): jcs211755
Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging
Provost J, Garofalakis A, Sourdon J, Bouda D, Berthon B, Viel T, Perez-Liva M, Lussey-Lepoutre C, Favier J, Correia M, Pernot M, Chiche J, Pouyssegur J, Tanter M, Tavitian B
Nat Biomed Eng 2(2): 85-94
The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma
Ambrosetti D, Dufies M, Dadone B, Durand M, Borchiellini D, Amiel J, Pouyssegur J, Rioux-Leclercq N, Pagès G, Burel-Vandenbos F
PLoS ONE 13(2): e0193477