Myc drives Pten/ p53-deficient proliferation and metastasis due to Il6-secretion and Akt- suppression via Phlpp2 RUNNING TITLE: Il6 drives Myc in Pten-mutant prostate metastasis
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چکیده
RUNNING TITLE: Il6 drives Myc in Pten-mutant prostate metastasis Dawid G. Nowak, Hyejin Cho , Tali Herzka , Kaitlin Watrud, Daniel V. DeMarco, Victoria M.Y. Wang, Serif Senturk, Christof Fellmann, David Ding, Tumas Beinortas, David Kleinman, Muhan Chen, Raffaella Sordella, John E. Wilkinson, Mireia Castillo-Martin, Carlos Cordon-Cardo, Brian D. Robinson & Lloyd C. Trotman* 1 Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724 2 Mirimus Inc., 1 Bungtown Road, Cold Spring Harbor, NY 11724 3 Department of Pathology, University of Michigan, Ann Arbor, MI 48109 4 Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 5 Department of Pathology, NewYork-Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10065 # equal contribution * correspondence: [email protected] The authors disclose no potential conflicts of interest
منابع مشابه
MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2.
UNLABELLED We have recently recapitulated metastasis of human PTEN/TP53-mutant prostate cancer in the mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by MYC, and not AKT, activation. Here, we show that cell-cell communication by IL6 drives the AKT-MYC switch through activation of the AKT-suppressing phosphatase PHLPP2, when PTEN and p53 are lost together, ...
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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 ...
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