Cells 2012, 1(4), 886-904; doi:10.3390/cells1040886
Article

Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway

1 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA 2 Division of Medical Genetics, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
* Author to whom correspondence should be addressed.
Received: 7 August 2012; in revised form: 11 October 2012 / Accepted: 12 October 2012 / Published: 19 October 2012
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Abstract: The MST/Salvador-Warts-Hippo and mTOR/Akt/PI3K growth signaling pathways have been established as important modulators of cell growth, proliferation and cell survival in controlling organ size in Drosophila and mammals. Here, we sought to determine the role of the MST family of kinases, some of which are components of the Hippo pathway, and their closely related Sterile 20-like kinases (STK) as candidates for mediating cross-talk between the Hippo and mTOR pathways. Expression analysis in the HepG2 and MCF7 cell lines demonstrated common expression of MST1/2/4, MAP4K3/4/5, STK 24 (MST3), STK25, STK39, Pak1, SLK, Stradα/β and TAO2. All components of the Hippo signaling pathway are present in both cell lines except for YAP1 in MCF7 cells. mTOR inhibition via rapamycin decreases TAZ levels in HepG2 but not MCF7 cells and increases TEAD1 levels in MCF7 but not HepG2 cells, suggesting a selective role of the mTOR pathway in regulating these Hippo targets in a cell type-specific manner. Furthermore, the cellular localization of TAZ changes in response to mTORC1/2 inhibitors and Akt inhibition. These findings demonstrate the mTOR-dependent regulation of Hippo signaling at the level of the transcriptional regulators TAZ and TEAD1 and highlight the potential role for mTOR inhibitors in regulating Hippo-signaling dependent tumors.
Keywords: Hippo pathway; mTOR pathway; Sterile-20 like kinase family; TAZ; TEAD1; signal transduction

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MDPI and ACS Style

Chiang, J.; Martinez-Agosto, J.A. Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway. Cells 2012, 1, 886-904.

AMA Style

Chiang J, Martinez-Agosto JA. Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway. Cells. 2012; 1(4):886-904.

Chicago/Turabian Style

Chiang, Jonathan; Martinez-Agosto, Julian A. 2012. "Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway." Cells 1, no. 4: 886-904.

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