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

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 whic...

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Autores principales: Chiang, Jonathan, Martinez-Agosto, Julian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901137/
https://www.ncbi.nlm.nih.gov/pubmed/24710534
http://dx.doi.org/10.3390/cells1040886
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author Chiang, Jonathan
Martinez-Agosto, Julian A.
author_facet Chiang, Jonathan
Martinez-Agosto, Julian A.
author_sort Chiang, Jonathan
collection PubMed
description 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.
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spelling pubmed-39011372014-04-07 Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway Chiang, Jonathan Martinez-Agosto, Julian A. Cells Article 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. MDPI 2012-10-19 /pmc/articles/PMC3901137/ /pubmed/24710534 http://dx.doi.org/10.3390/cells1040886 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Chiang, Jonathan
Martinez-Agosto, Julian A.
Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title_full Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title_fullStr Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title_full_unstemmed Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title_short Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway
title_sort effects of mtor inhibitors on components of the salvador-warts-hippo pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901137/
https://www.ncbi.nlm.nih.gov/pubmed/24710534
http://dx.doi.org/10.3390/cells1040886
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