Deborah Altomare, Ph.D.
Fox Chase Cancer Center
AKT Function in Ovarian Tumor Cell Invasiveness and In Vivo Pathogenesis
Project Summary
The high morbidity of ovarian cancer is largely attributed to the rapid proliferation of tumor cells, with spreading or dissemination to multiple abdominal organs. Although the biological steps for tumor spreading or metastasis are known, the molecular and signaling events that are important in this process are still largely unknown.
One central player in several hallmark pathways important for both tumor growth and progression is the AKT kinase. We and others have shown that all three AKT kinases, designated AKT1, AKT2 and AKT3, are frequently activated in ovarian tumors. However, in order to fully capitalize on the benefits of therapeutically targeting components of the AKT pathway, many questions remain regarding the essential role of AKT to specific stages of ovarian tumor progression, and whether AKT1 or AKT2 isoforms might differentially regulate particular stages of ovarian pathogenesis.
The objective of this proposal is to provide an improved understanding of how different AKT isoforms cooperate with other molecular perturbations to facilitate tumor cell proliferation, survival and/or metastasis. Both human ovarian cancer cells and genetically defined mouse models will be used to provide mechanistic rationale for the role of AKT activation in ovarian cancer progression. It is expected that new insights into how to control or target metastatic spread of the disease may eventually lead to improved patient prognosis.
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