Project 467042

In recent years, DEP-domain containing mTOR-interacting protein (Deptor) has been identified as an endogenous inhibitor of mammalian target of Rapamycin (mTOR), the master regulator of cellular growth which is frequently dysregulated in cancers. Deptor plays pivotal roles in the regulation of cell proliferation and survival, and efforts to elucidate the mechanisms by which it exerts its effects in cancer have mainly focused on its direct interactions with mTOR. However, while clinically, high mTOR complex 1 (mTORC1) activity corresponds with poor prognoses among cancer patients, consistent with low Deptor levels frequently reported in most tumors, paradoxically, high expression of Deptor in human breast cancer also corresponds with the worst prognoses in these patients. These findings point to a dual role for Deptor in cancer, and potential pro-tumorigenic functions independent of mTORC1. Thus, my research aims to expand understanding of Deptor and its potential interactors, with its seemingly contradictory contributions in tumorigenesis, and characterize the role Deptor plays in breast cancer initiation and progression, using conditional Deptor knockout transgenic mouse models of breast cancer. Greater understanding of mTOR modulation is necessary to improve clinical interventions involving the mTOR pathway, and considering the ubiquity of mTOR dysregulation in various cancers, understanding the functions and regulatory mechanisms of mTOR components such as Deptor is an important step in the advancement of cancer research and treatment. Further, by investigating Deptor's role independent of mTOR the proposed research will unveil the scope of a newly discovered but widely acting player in cancer and its potential as a novel target in anticancer therapeutics.