Akt mediates metastasis-associated gene 1 (MTA1) regulating the expression of E-cadherin and promoting the invasiveness of prostate cancer cells.
Akt mediates metastasis-associated gene 1 (MTA1) regulating the expression of E-cadherin and promoting the invasiveness of prostate cancer cells.
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Akt 介导转移相关基因 1 (MTA1) 调节 E-钙粘蛋白表达并促进前列腺癌细胞侵袭
DOI：
10.1371/journal.pone.0046888
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Wang H;Fan L;Wei J;Weng Y;Zhou L;Shi Y;Zhou W;Ma D;Wang C
人转移相关基因1 （MTA1）与前列腺癌转移高度相关；然而，MTA1促进转移的分子功能尚不清楚。在本研究中，我们证明通过siRNA处理MTA1沉默，通过磷酸化AKT （p-AKT）导致E-cadherin表达上调，并降低前列腺癌细胞的侵袭性。我们发现MTA1在超过90%的前列腺癌组织中表达，尤其是转移性前列腺癌组织，而在正常前列腺组织中不表达。RT-PCR和Western blot分析显示，MTA1在高转移性前列腺癌PC-3M-1E8细胞（1E8）中的表达明显高于低转移性前列腺癌PC-3M-2B4细胞（2B4）。通过siRNA处理沉默MTA1在1E8细胞中的表达，增加了细胞的恶性特征，包括细胞粘附能力，降低了细胞的侵袭能力，改变了细胞骨架的极性。过表达MTA1的1E8细胞E-cadherin表达降低，而MTA1 siRNA处理的1E8细胞E-cadherin表达升高。磷酸化AKT （p-AKT）的表达或wortmannin处理（100 nM）对p-AKT的抑制显著改变了MTA1调节E-cadherin表达的功能。E-cadherin表达的改变改变了p-AKT在细胞恶性特征中的作用。这些结果表明MTA1通过p-AKT/E-cadherin通路在控制前列腺癌细胞恶性转化中发挥重要作用。本研究也为MTA1调控前列腺癌转移提供了新的机制。
Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis.
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影响因子：
11.2
作者：
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通讯作者：
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DOI：
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DOI：
10.1073/pnas.0905349106
发表时间：
2009-07-14
影响因子：
11.1
作者：
Katsamba, P.;Carroll, K.;Honig, Barry H.
通讯作者：
Honig, Barry H.