PP2A as a component of negative feedback loops: role in cancer developmement progression.

Cancer is essentially a disease of disturbed signaling. The existence of negative feedback loops predicts that both oncogenic kinases should be activated and tumor suppressive phosphatases should be inactivated to promote full-blown cell transformation. The tumor suppressor protein phosphatase 2A (PP2A) contributes to regulation of multiple negative feedback loops. In this project, we will identify and analyze the role of clinically-relevant PP2A-oncogene feedback loops in cancer development using in vitro models of human cell transformation and in vivo PP2A KO mice. The results of proposed studies will provide essential insights into mechanisms of PP2A tumor suppressor function, generate improved in vitro and in vivo models of cell transfromation for preclinical studies and suggest novel therapeutic strategies targeting these oncogene-PP2A feedback loops.

Keywords:PP2A, Cancer, Negative feedback loops

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences