Suppression of Akt1-β-catenin pathway in advanced prostate cancer promotes TGFβ1-mediated epithelial to mesenchymal transition and metastasis.
Suppression of Akt1-β-catenin pathway in advanced prostate cancer promotes TGFβ1-mediated epithelial to mesenchymal transition and metastasis.
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晚期前列腺癌中 Akt1-β-catenin 通路的抑制促进 TGF beta 1 介导的上皮间质转化和转移
DOI：
10.1016/j.canlet.2017.05.028
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发表时间：
2017-08-28
期刊：
影响因子：
9.7
通讯作者：
Somanath PR
中科院分区：
文献类型：
--
作者：
Gao F;Alwhaibi A;Sabbineni H;Verma A;Eldahshan W;Somanath PR
AKT1对于各种癌症的致癌转化和肿瘤的生长至关重要i是，三氯替替氨酸（TCBN）介导的Akt抑制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 improved expression of epithelial marker E-cadherin in TRAMP prostate, and in PC3 and DU145 cells. Next, we identified that PCA细胞中的AKT1敲低导致TGFβ1的产生及其受体TGFβRII，与β-catenin的表达降低有关，pCA细胞用ICG001处理β-catenin catenin to the n-cadherin的表达，以β-catenin的核易位。
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 TGFβ1 and its receptor TGFβ RII, associated with a decreased expression of β-catenin. Furthermore, treatment of PCa cells with ICG001 that blocks nuclear translocation of β-catenin promoted EMT and N-cadherin expression. Together, our study demonstrates a novel role of the Akt1-β-catenin-TGFβ1 pathway in advanced PCa.
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影响因子：
7.3
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通讯作者：
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影响因子：
8
作者：
Gao, Fei;Artham, Sandeep;Sabbineni, Harika;Al-Azayzih, Ahmad;Peng, Xiao-Ding;Hay, Nissim;Adams, Ralf H.;Byzova, Tatiana V.;Somanath, Payaningal R.
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Gao D
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作者：
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通讯作者：
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