BMK1 kinase suppresses epithelial-mesenchymal transition through the Akt/GSK3β signaling pathway.
BMK1 kinase suppresses epithelial-mesenchymal transition through the Akt/GSK3β signaling pathway.
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DOI：
10.1158/0008-5472.can-11-2055
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发表时间：
2012-03-15
期刊：
影响因子：
11.2
通讯作者：
Lee JD
中科院分区：
文献类型：
--
作者：
Chen R;Yang Q;Lee JD
Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of cancer metastasis. The MAP kinases ERK, JNK and p38 have been implicated in promoting EMT, but a role for the MAP kinase BMK1 has not been studied. Here we report that BMK1 signaling suppresses EMT. BMK1 elevation augmented E-cadherin-mediated cell-cell adhesion, downregulated mesenchymal markers and decreased cell motility. Conversely, BMK1 silencing attenuated E-cadherin-mediated cell-cell adhesion, upregulated mesenchymal markers and stimulated cell motility. BMK1 depletion dramatically increased the accumulation of endogenous Snail in the nuclear compartment. Snail accumulation was mediated by Akt/GSK3β signaling, which was activated by a modulation in the expression of the mTOR inhibitor DEPTOR. In support of these observations, BMK1 depletion promoted metastasis in vivo. Together, our findings reveal a novel mechanism of EMT control via mTOR/Akt inhibition that suppresses cancer metastasis.
