Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression.
Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression.
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DOI：
10.1016/j.ccr.2011.07.013
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发表时间：
2011-08-16
期刊：
影响因子：
50.3
通讯作者：
Trotman LC
中科院分区：
文献类型：
--
作者：
Chen M;Pratt CP;Zeeman ME;Schultz N;Taylor BS;O'Neill A;Castillo-Martin M;Nowak DG;Naguib A;Grace DM;Murn J;Navin N;Atwal GS;Sander C;Gerald WL;Cordon-Cardo C;Newton AC;Carver BS;Trotman LC
PI3-Kinase/AKT通路的过度激活是许多癌症的驱动力。在这里，我们确定AKT失活的磷酸酶PHLPP1是一种前列腺癌抑制因子。我们发现，PHLPP1缺失会导致小鼠前列腺癌的发生，在部分缺失Pten的情况下，还会导致肿瘤。这种遗传环境最初通过P53和Phlpp2同源基因触发生长抑制反应，并揭示了TrP53的自发失活是全面疾病的一种条件。令人惊讶的是，患者样本中PTEN和PHLPP1的共同缺失高度限于转移性疾病，并与TP53和PHLPP2的缺失密切相关。这些数据建立了PTEN突变前列腺癌进展为威胁生命的疾病的概念性框架。
Hyper-activation 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, upon 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 co-deletion 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.
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影响因子：
30.8
作者：
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Carver, Brett S.;Tran, Jennifer;Chen, Zhenbang;Carracedo-Perez, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Gopalan, Anuradha;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
7.3
作者：
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通讯作者：
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影响因子：
50.3
作者：
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通讯作者：
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