Group leader: Stress responses and Cancer
Moorenstraße 5 40225 Düsseldorf
Brain tumors are highly dependent on glucose to develop. However, brain tumors are confronted to glucose-deprived conditions within their microenvironment as a consequence of high glucose consumption and poor nutrient supply. Adversely, these conditions may favor the emergence of highly aggressive cancer cell clones, as a result of cellular adaptation to such stress. The aim of our research is to understand how brain cancer cells respond and adapt to glucose deprivation, and how this is clinically relevant.
The main focus of our laboratory is to identify and characterize the mechanisms of tumor adaptation to glucose deprivation stress in medulloblastoma and glioblastoma. This encompasses investigating the role of cell signaling pathways, regulators of mRNA translation, and long non-coding RNAs in such a context. We are using a wide range of molecular biology and cellular biology techniques to functionally decipher the role of protein and RNA candidates in the response to glucose deprivation in brain cancer models.
- Varon M, Levy T, Mazor G, Ben David H, Marciano R, Krelin Y, Prasad M, Elkabets M, Pauck D, Ahmadov U, Picard D, Qin N, Borkhardt A, Reifenberger G, Leprivier G, Remke M, Rotblat B.
The long noncoding RNA TP73-AS1 promotes tumorigenicity of medulloblastoma cells. Int J Cancer, 2019 May 13. PubMed
- Lim JKM, Delaidelli A, Minaker SW, Zhang HF, Colovic M, Yang H, Negri GL, von Karstedt S, Lockwood WW, Schaffer P, Leprivier G*, Sorensen PH*.
Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance. Proc Natl Acad Sci U S A, 2019 May 7;116(19):9433-9442. *Co-senior authorship. PubMed
- Mazor G, Levin L, Picard D, Ahmadov U, Carén H, Borkhardt A, Reifenberger G, Leprivier G, Remke M, Rotblat B.
The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells. Cell Death Dis, 2019 Mar 13;10(3):246. PubMed
- Delaidelli A, Gian Luca Negri GL, Asad Jan A, Khan D, Jansonius B, Htoo Zarni Oo HZ, El-Naggar A, Carnie CJ, Remke M, Maris JM, Leprivier G, Sorensen PH.
MYCN amplified neuroblastoma requires the mRNA translation regulator eEF2 kinase to adapt to nutrient deprivation. Cell Death Differ, 2017 Sep;24(9):1564-1576. PubMed
- Rotblat B*, Grunewald TG*, Leprivier G*, Melino G, Knight RA.
Anti-oxidative stress response genes: bioinformatic analysis of their expression and relevance in multiple cancers. Oncotarget, 2013 Dec;4(12):2577-90. *These authors contributed equally to the work. PubMed
- Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Somasekharan SP, Faubert B, Bridon G, Tognon CE, Mathers J, Thomas R, Li A, Barokas A, Kwok B, Bowden M, Smith S, Wu X, Korshunov A, Hielscher T, Northcott PA, Galpin JD, Ahern CA, Wang Y, McCabe MG, Collins VP, Jones RG, Pollak M, Delattre O, Gleave ME, Jan E, Pfister SM, Proud CG, Derry WB, Taylor MD, Sorensen PH.
The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell, 2013 May 23;153(5):1064-79. PubMed
- Ng TL, Leprivier G, Robertson MD, Chow C, Martin MJ, Laderoute KR, Davicioni E, Triche TJ, Sorensen PH.
The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death Differ, 2012 Mar;19(3):501-10. PubMed
- Leprivier G, Baillat D, Begue A, Hartmann B, Aumercier M.
Ets-1 p51 and p42 isoforms differentially modulate Stromelysin-1 promoter according to induced DNA bend orientation. Nucleic Acids Res, 2009 Jul; 37(13): 4341-52. PubMed
- Laitem C*, Leprivier G*, Choul-Li S, Begue A, Monte D, Larsimont D, Dumont P, Duterque-Coquillaud M, Aumercier M.
Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51. Oncogene, 2009 May 21; 28(20): 2087-99. *These authors contributed equally to the work. PubMed
- Baillat D*, Leprivier G*, Régnier D, Vintonenko N, Bègue A, Stéhelin D, Aumercier M.
Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Ets binding sites present in the promoter. Oncogene, 2006 Sep 21; 25(42): 5764-76.*These authors contributed equally to the work. PubMed