BMK1 kinase suppresses epithelial-mesenchymal transition through the Akt/GSK3β signaling pathway.

Abstract

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of cancer metastasis. The mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase, c-jun-NH(2)-kinase, 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.

DOI: 10.1158/0008-5472.CAN-11-2055

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@article{Chen2012BMK1KS, title={BMK1 kinase suppresses epithelial-mesenchymal transition through the Akt/GSK3β signaling pathway.}, author={Runqiang Chen and Qingkai Yang and Jiing-Dwan Lee}, journal={Cancer research}, year={2012}, volume={72 6}, pages={1579-87} }