Targeting the Interaction of the p53 gene and Focal Adhesion Kinase (FAK) as a Possible Therapeutic Aagent

FAK is phosphorylated kinase involved in a variety of biological processes such as adhesion, motility, survival, and proliferation, metastasis, invasion and angiogenesis, and was recently established as a key component of the signal transduction pathways triggered by integrins. For the purposes of this research, the importance of FAK regarding invasion and cell survival will be assayed.

Cancerous cells often display anomalies in the processes described above. In tumor and metastatic tissue, an increase in FAK mRNA levels has been observed. This increased expression can also be detected in pre-malignant tissues. Moreover, it has been proven that inhibition of FAK in FAK-proficient invasive cancer cells prevented cell invasion and metastasis. Regarding survival, FAK has been linked to anoikis. These results suggest that FAK can be a useful marker for detection of irregularities in cells that may develop into a cancer. To better understand the role of FAK in carcinogenesis, the FAK promoter was cloned. Interestingly, it was found to contain p53 binding sites. P53 is a tumor suppressor gene. It is known that the p53 gene is the location at which most genetic alterations in human mutations occur, being mutated in almost 50% of all tumors and up to 75% in invasive cancers.

It has already been demonstrated that p53 can bind to the FAK promoter and inhibit its transcriptional activity. We will screen for drugs that target FAK and p53 in different cancers by performing MTT assays. The MTT assays will help us determine the number of viable cells in a given culture. This will tell us if the drugs have an impingement on the interaction of the p53 and FAK proteins.Text