@article{ecc3d36867ba418db1546d55817a2afe,
title = "Identification of PHLPP1 as a Tumor Suppressor Reveals the Role of Feedback Activation in PTEN-Mutant Prostate Cancer Progression",
abstract = "Hyperactivation of the PI 3-kinase/AKT pathway is a driving force of many cancers. Here we identify the AKT-inactivating phosphatase PHLPP1 as a prostate tumor suppressor. We show that Phlpp1-loss causes neoplasia and, on partial Pten-loss, carcinoma in mouse prostate. This genetic setting initially triggers a growth suppressive response via p53 and the Phlpp2 ortholog, and reveals spontaneous Trp53 inactivation as a condition for full-blown disease. Surprisingly, the codeletion of PTEN and PHLPP1 in patient samples is highly restricted to metastatic disease and tightly correlated to deletion of TP53 and PHLPP2. These data establish a conceptual framework for progression of PTEN mutant prostate cancer to life-threatening disease.",
author = "Muhan Chen and Pratt, {Christopher P.} and Zeeman, {Martha E.} and Nikolaus Schultz and Taylor, {Barry S.} and Audrey O'Neill and Mireia Castillo-Martin and Nowak, {Dawid G.} and Adam Naguib and Grace, {Danielle M.} and Jernej Murn and Nick Navin and Atwal, {Gurinder S.} and Chris Sander and Gerald, {William L.} and Carlos Cordon-Cardo and Newton, {Alexandra C.} and Carver, {Brett S.} and Trotman, {Lloyd C.}",
note = "Funding Information: We thank S. Lowe, S. Powers, M. Zhang, K. Maimer, J. Hicks, M. Spector, J. Zuber, and W. Xue for discussion, help with analyses, and reagents, L. Bianco, A. Nourjanova, K. Manova, and A. Barlas for help with histology procedures and analysis, R. McCombie and S. Muller for help with sequencing, M. Hammell, W. Luo, and C. Johns for discussion and help with RNA expression array production and evaluation, and J. Simon and M. Taylor for discussion of animal procedures. This work was supported by grants to L.C.T. from the Department of the Army (W81XWH-09-1-0557), the Starr Foundation (I3-A154), the V Foundation, the V Kann Rasmussen Foundation (VKRF), and the NIH (1R01CA137050-01A2), as well as by the MSKCC Prostate SPORE and NIH grant GM-43154 to A.C.N. L.C.T. is a Rita Allen Foundation Scholar and would like to dedicate this work to the memory of William L. Gerald. ",
year = "2011",
month = aug,
day = "16",
doi = "10.1016/j.ccr.2011.07.013",
language = "English (US)",
volume = "20",
pages = "173--186",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}