Turning Reciprocal Feedback Regulation into Combination Therapy Timothy C. Thompson  Cancer Cell  Volume 19, Issue 6, Pages 697-699 (June 2011) DOI: 10.1016/j.ccr.2011.05.022 Copyright © 2011 Elsevier Inc. Terms and Conditions

Figure 1 Reciprocal Inhibition Feedback Links AR- and PTEN Loss/PI3K-AKT Signaling Pathways in Prostate Cancer As reported in Carver et al. (2011) and Mulholland et al. (2011), reciprocal negative feedback underlies the oncogenic activities of PTEN loss/PI3K-AKT signaling (depicted as the area inside the dotted “corners”). Activation of PI3K-AKT leads to suppression/subversion of AR signaling through suppression of HER kinases; upregulation of EGR1 and c-JUN transcriptional coregulators; and upregulation of the Polycomb group protein EZH2. Reciprocal negative feedback is established, in part, through AR-stimulated, FKBP5-mediated activation of AKT phosphatase PHLPP. GFs, growth factors. Cancer Cell 2011 19, 697-699DOI: (10.1016/j.ccr.2011.05.022) Copyright © 2011 Elsevier Inc. Terms and Conditions