Oxygen Sensing and Cancer Group

Susanne Schlisio
Ludwig Institute for Cancer Research Ltd
Karolinska Institutet
Box 240
SE-171 77 Stockholm
Sweden

Visiting Address: Nobels Väg 3

Phone: +46 8 524 871 17
Fax: +46 8 33 28 12

S. Schlisio  Ph.D., Assistant Member

The focus of our research concerns the mechanisms of how disruption of oxygen-sensing pathways can lead to cancer. Oxygen sensors enable the cell to adapt to low oxygen environments and are also critical for normal development and apoptosis. These events are often disrupted in the development of tumors. Oxygen sensing is mediated partly via prolyl hydroxylases that require molecular oxygen for enzymatic activity. Our work specifically focuses on how prolyl hydroxylases execute apoptosis in neural precursors during development and how disruption of this process can lead to certain forms of nervous system tumors.

We are now working to connect the function of the prolyl hydroxylases with cancer metabolism. Hydroxylase activity is dependent upon metabolites that take part in the Krebs cycle. This dependency ties these enzymes directly into the metabolic network. Inactivation of the Krebs cycle enzyme Succinate Dehydrogenase, a bona fide tumor suppressor, leads to enzymatic inactivation of the prolyl hydroxylases. Decreased Krebs cycle activity is a cancer-specific phenomenon. In 1924, Otto Warburg observed that cancer cells are highly glycolytic in the presence of oxygen and have reduced rates of oxidative phosphorylation. An attractive hypothesis is that the cancer cells favor “pseudo-hypoxia” in order to escape oncogene-induced apoptosis and senescence. Our future work will focus on cancer metabolism and its direct impact on the prolyl hydroxylase function.

Postdoctoral position open for application

The Group

• Bergström, Anita   Senior Technician
  
• Fell, Stuart   Ph.D. Student
  
• Chen, Zhi Xiong  Postdoctoral Fellow
  
• Cai, Yujia  Ph.D. Student
  

Selected Publications

• Schlisio S. Neuronal Apoptosis by Prolyl Hydroxylation: Implication in Nervous System Tumors and the Warburg Conundrum J Cell Mol Med. 2009 Aug 19. [Epub ahead of print]
• Schlisio S, Kenchappa RS, Vredeveld LCW, George RE, Stewart R, Shahriari K , Greulich H, Nguyen VN, Dahia PL, Pomeroy S, Maris JM, Look TA, Meyerson M, Peeper DS, Carter BD and Kaelin WG. The Kinesin Gene KIF1Bß Acts Downstream of EglN3 to Induce Apoptosis and is a Potential 1p36 Tumor Suppressor. Genes Dev. 2008 Apr 1;22(7):884-93
• Lee S, Nakamura E, Wei W, Linggi MS, Sajan MP, Farese RV, Freeman RS, Carter BD, Kaelin WG and Schlisio S. (2005) Neuronal Apoptosis linked to EglN3 Prolyl Hydroxylase and Familial Pheochromocytoma Genes. Developmental Culling and Cancer. Cancer Cell, August 2005, Vol. 8.
• Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S and Kaelin WG. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008 Feb 24;