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The role of ROS/RNS during inflammation-associated and sporadic carcinogenesis

Objective

"A link between inflammation and cancer has been suspected over a long period of time and in recent years genetic evidence supporting such notion could be obtained. Several signaling pathways, such as NF-κB and STAT3, could be identified by our group as well as other groups to play important roles during tumor promotion and progression. Chronic inflammation leads to the formation of reactive oxygen and nitrogen species, which are known to cause DNA damage and inactivation of DNA repair mechanisms, thereby presumably inducing tumor-initiating mutations. On the other hand, oxidative stress has been documented to trigger apoptosis and cellular senescence. However, in vivo evidence demonstrating the consequences of increased oxidative stress on tumor development in a distinct genetic model is lacking. Selenoproteins of the glutathione peroxidase and thioredoxin reductase family are important anti-oxidant scavenger systems. Using cell type specific inactivation (epithelial cells an myeloid cells) of several of these family members in various well established and relevant models of inflammation-associated and sporadic colon tumorigenesis we will directly examine the role of these anti-oxidant systems. These models will allow us to genetically determine the outcome of increased lipid peroxidation and accumulation of reactive oxygen species in each cell type and to address whether cancer development is supported or inhibited under such conditions and will help to identify which phase of tumor development is affected. Furthermore, we expect to obtain results that will determine whether increased levels of ROS/RNS found during chronic inflammation are capable of initiating tumorigenesis. Our proposed experiments are supposed to provide fundamental insight into the molecular changes in the tumor microenvironment, which will ultimately help to identify novel strategies to prevent and treat colorectal cancer."

Field of science

  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/cancer/colorectal cancer

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG
Address
Paul Ehrlich Strasse 42-44
60596 Frankfurt
Germany
Activity type
Research Organisations
EU contribution
€ 1 038 672,25
Principal investigator
Florian Greten (Prof.)
Administrative Contact
Robert Dornberger (Mr.)

Beneficiaries (2)

CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG
Germany
EU contribution
€ 1 038 672,25
Address
Paul Ehrlich Strasse 42-44
60596 Frankfurt
Activity type
Research Organisations
Principal investigator
Florian Greten (Prof.)
Administrative Contact
Robert Dornberger (Mr.)
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Participation ended

Germany
EU contribution
€ 461 327,78
Address
Ismaninger Strasse 22
81675 Muenchen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Inge Linder (Ms.)