Grant: Travel Awards - Institute Community Support

Increase of free oygen radicals (Reactive oxygen species (ROS)) is a natural by- product of normal cell metabolism, but can also be generated by the cells itself (de novo) by specialized enzymes known as the NADPH oxidases (NOXs). Cellular transformation can be caused by numerous genes with the potential to turn a normal cell into a cancer cell (proto-oncogenes). These oncogenes include activated Receptor tyrosine kinases (RTKs), K-Ras, H-Ras, c-Met, c-Myc, and c-Src, and transformation by these oncogenes is consistently associated with elevated ROS levels. Excessive ROS production drives cellular proliferation by nuclear cell cycle controlling proteins (D-type cyclins) and is widely associated with the transformation of cytosolic oncogenes such as K-Ras or Src. Constitutive high ROS is damaging to vital cellular components such as proteins, lipids and DNA with a potential of enhancing the cellular transformation into an advanced cancerous stage. Little is known about ROS' role in oncogenic RTK signaling, which are critical players in several biological cell processes and highly regulated potent proto-oncogenes. RTKs permit the transmission of information from outside the cell into the cytoplasm and nucleus in signaling transduction pathways activating a myriad of proteins with the capability to activate genes (transcription factors). RTKs are involved in cell survival, however they frequently undergo mutations or structural alterations causing oncogenic activation in human malignancies. As canonical RTK signaling involves Ras and has been shown to induce cyclin D1 mediated proliferation, I speculate that ROS might play a role in this signaling network. My research hypothesis is that ROS is instrumental for cellular transformation by oncogenic RTK and that the RTK-driven ROS generation is tightly regulated through specific signaling events in the cells.