Funding outcome

Ovarian cancer is the leading cause of gynecological cancer death in women. The movement of ovarian cancer cells to new sites in the body, known as metastasis, is the major cause of death among ovarian cancer patients. Two types of proteins known as tumor/metastasis suppressors and tumor/metastasis promoters regulate cancer formation and progression to metastasis. Preventing the activation or inactivation of these proteins is a promising treatment strategy for the interruption of the metastatic process. In spite of significant advances in the field of cancer diagnosis and treatment, currently, there are no effective therapies to prevent ovarian cancer spread and recurrence. p53 is a well-known tumor/metastasis suppressor protein that regulates the expression of many other proteins that are involved in cancer development and metastasis. p53 is inactive/altered in more than 50% of all cancers and over 80% of metastatic tumors. Furtheremore, p53 is altered in 90% of the most common type of ovarian tumors and has well documented role in both initiation of ovarian cancer and its metastatic progression. To function effectively, p53 associates with other proteins. Plakoglobin is another tumor/metastasis suppressor that we have shown to associate with normal as well as a number of most frequently altered p53. In addition, its interaction with altered p53 can restore the normal tumor suppressor function of this protein. Plakoglobin and p53 cooperate to regulate a wide range of physiological functions involved in the inhibition of cancer cell growth and metastasis. In the present study, we will elucidate mechanisms through which p53 and plakoglobin suppress tumor formation and progression. This will identify proteins that are regulated by p53 and plakoglobin and contribute to the process of ovarian cancer development and metastasis. We will confirm the results of our experimental studies by examining patient biopsies and correlating the results with disease-free and overall survival of the patients. The identified proteins can be used to develop therapeutics. The ultimate goal of our project is to identify molecules that can serve as therapeutic targets for designing novel, specific and effective treatment plans for patients with ovarian cancers.