Oparka 2014 Abstract MiP2014
|Investigation of the mitochondrial functions to understand p66Shc and reactive oxygen species interplay in tumor cells.|
Alternations of pivotal mitochondrial function – oxidative phosphorylation as well as abnormal cellular ROS production - can potentially be responsible for pathogenesis of cancer. In the last years, implications of p66Shc adaptor protein in the cellular response to oxidative stress have been discovered. Involvement of this protein in cell death is related to oxidative stress. Phosphorylation of p66Shc at Ser36 can be activated by extracellular or intracellular reactive oxygen species (ROS), and an initiated cascade of events is finally involved in the amplification of mitochondrial ROS production.
The available literature does not contain a lot of data concerning the role of p66shc and its Ser36 phosphorylation in tumorigenesis and cancer growth. Therefore, we studied the relationship between ROS production, antioxidant defense systems and the level of p66Shc as well as p66Shc phosphorylation in murine cancer cell lines, derived from ectoderm (B16-F10, B78, MmB16, EMT6, 4T1), mesoderm (Renca) and endoderm (CT26.WT, Hepa1-6, LLC, Panc02).
The cancer cells exhibited various levels of p66Shc and its Ser36 phosphorylation, which simultaneously is negatively correlated with the level of superoxide dismutase 2 in some of the investigated cancer cell lines.
ROS can mediate opposing cellular functions like cell proliferation and apoptosis. In turn, p66Shc Ser36 phosphorylation pathway is involved in regulation of mitochondrial metabolism and is responsible for elevated intracellular ROS levels. Moreover, p66Shc seems to play an important role in cancer metastasis and cancer cell adhesion. This emphasizes the importance of understanding the mechanisms and sites of ROS formation in cancer cells, the role of p66Shc in this process and the effect on tumor physiology.
Supported by Statutory Founding from Nencki Institute of Experimental Biology and Polish Ministry of Science and Higher Education grant W100/HFSC/2011.
Labels: MiParea: Respiration Pathology: Cancer Stress:Oxidative stress;RONS Organism: Human
Event: B2, Oral MiP2014
Dep Biochem, Nencki Inst Experim Biol, Warsaw, Poland. – email@example.com