Autor: |
Lloyd C. Trotman, Brian D. Robinson, Carlos Cordon-Cardo, Mireia Castillo-Martin, John E. Wilkinson, Raffaella Sordella, Muhan Chen, David Kleinman, Tumas Beinortas, David Ding, Christof Fellmann, Serif Senturk, Victoria M.Y. Wang, Daniel V. DeMarco, Kaitlin Watrud, Tali Herzka, Hyejin Cho, Dawid G. Nowak |
Rok vydání: |
2023 |
Popis: |
Supplementary Figure S7. Pathway to Pten/ Trp53 deficient prostate metastasis and therapy resistance. Pten-loss triggers PIP3 signaling to activate AKT, which prompts activation of the p53/ p21/ p16 tumor suppressors and senescence arrest. Suppression and loss of p53 in this context results in cell proliferation and Il6 secretion. Il6 signals both auto and paracrine to activate Myc via the Jak/Stat pathway. Myc induces the Phlpp2 phosphatase which creates a negative feedback loop by dampening Akt activation. Metastases (and castration-resistant tumors) select for increased Myc expression (and gene amplification, and Akt inactivation, demonstrating that Myc supersedes the need for Akt in lethal prostate cancer. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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