Role of KRAS mutations in the collective motility and invasion of tumor cells
KRAS is one of the most frequent oncogenic mutation in human tumors. As RAS participates in several growth factor-induced signaling pathways, tumors carrying the KRAS mutation tend to be more aggressive and resistant to traditional therapies. In addition to the well described RAS-RAF-MAPK signaling, the mutant RAS also activates the PI3K-AKT, PLC-PKC and JAK-STAT pathways.
The collaboration between researchers at Semmelweiss and Eotvos Universities are highly synergystic: Dr Timar's group develops model cell lines and characterizes their in vivo behavior and pathology. Dr Czirok's group establishes mathematical models of signal transduction pathways and performs sensitive in vitro assays to access the cells' collective migration and invasion ability.
We will investigate the functional role of KRAS mutations in collective motility and cell adhesivity using in vitro imaging and automatic cell tracking techniques. We will identify the contribution of various signaling pathways by specific pharmacological inhibitors. The project will hopefully yield clinically relevant results and may establish the base to a rational design of compounds naturalizing the effects of mutant KRAS variants.