Research Summary

Role of Ras effector - Ras Association (RalGDS/AF-6) Domain Family Member in Tumor Invasion and Migration

Cancer is a disease of heterogeneous cell populations, with acquisition of genetic/epigenetic alterations in developmental pathways contributing to the initiation and progress of the disease. Several of these pathways are known, but the contribution of cellular context defined by other signaling molecules is not clear. Tumor microenvironment interaction with tumor is identified as critical contributor to the pathology of disease. However, the cellular and molecular players involved are only beginning to be understood. Oncogenic activation of Ras family of proteins, which regulate normal development, is frequently (~30-60%) detected in several types of cancer. Ras association (RalGDS/AF-6) domain family (RASSF) proteins are non-enzymatic effectors of Ras with both tumor suppressive and/or oncogenic functions. Differential expression of RASSF7 as well as few mutations in its open reading frame is observed in certain cancer tissues. Using this paradigm of RASSF7 expression in tumor, I will first probe the contribution of such effectors to tumor cell migration and invasion across the endothelium. Secondly, set up a tumor cell-niche model system to study the signaling pathways which govern these interactions. Subsequently, I will dissect key interacting pathways which can be extended to in vivo tumor invasion and metastasis in a mouse model and patient samples.

 

Figure Legend: Role of RASSF in tumor cell interaction with endothelium during tumor cell migration and invasion