| First Author | Gao F | Year | 2017 |
| Journal | Cancer Lett | Volume | 402 |
| Pages | 177-189 | PubMed ID | 28602980 |
| Mgi Jnum | J:243283 | Mgi Id | MGI:5908052 |
| Doi | 10.1016/j.canlet.2017.05.028 | Citation | Gao F, et al. (2017) Suppression of Akt1-beta-catenin pathway in advanced prostate cancer promotes TGFbeta1-mediated epithelial to mesenchymal transition and metastasis. Cancer Lett 402:177-189 |
| abstractText | Akt1 is essential for the oncogenic transformation and tumor growth in various cancers. However, the precise role of Akt1 in advanced cancers is conflicting. Using a neuroendocrine TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, we first show that the genetic ablation or pharmacological inhibition of Akt1 in mice blunts oncogenic transformation and prostate cancer (PCa) growth. Intriguingly, triciribine (TCBN)-mediated Akt inhibition in 25-week old, tumor-bearing TRAMP mice and Akt1 gene silencing in aggressive PCa cells enhanced epithelial to mesenchymal transition (EMT) and promoted metastasis to the lungs. Mechanistically, Akt1 suppression leads to increased expression of EMT markers such as Snail1 and N-cadherin and decreased expression of epithelial marker E-cadherin in TRAMP prostate, and in PC3 and DU145 cells. Next, we identified that Akt1 knockdown in PCa cells results in increased production of TGFbeta1 and its receptor TGFbeta RII, associated with a decreased expression of beta-catenin. Furthermore, treatment of PCa cells with ICG001 that blocks nuclear translocation of beta-catenin promoted EMT and N-cadherin expression. Together, our study demonstrates a novel role of the Akt1-beta-catenin-TGFbeta1 pathway in advanced PCa. |
