Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields

Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics...

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Autores principales: Jinesh, Goodwin G., Taoka, Rikiya, Zhang, Qiang, Gorantla, Siddharth, Kamat, Ashish M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819220/
https://www.ncbi.nlm.nih.gov/pubmed/27040869
http://dx.doi.org/10.1038/srep23965
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author Jinesh, Goodwin G.
Taoka, Rikiya
Zhang, Qiang
Gorantla, Siddharth
Kamat, Ashish M.
author_facet Jinesh, Goodwin G.
Taoka, Rikiya
Zhang, Qiang
Gorantla, Siddharth
Kamat, Ashish M.
author_sort Jinesh, Goodwin G.
collection PubMed
description Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47(phox) interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47(phox) interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47(phox) interaction are valid therapeutic targets to block transformation from blebbishields.
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spelling pubmed-48192202016-04-06 Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields Jinesh, Goodwin G. Taoka, Rikiya Zhang, Qiang Gorantla, Siddharth Kamat, Ashish M. Sci Rep Article Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47(phox) interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47(phox) interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47(phox) interaction are valid therapeutic targets to block transformation from blebbishields. Nature Publishing Group 2016-04-04 /pmc/articles/PMC4819220/ /pubmed/27040869 http://dx.doi.org/10.1038/srep23965 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Jinesh, Goodwin G.
Taoka, Rikiya
Zhang, Qiang
Gorantla, Siddharth
Kamat, Ashish M.
Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title_full Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title_fullStr Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title_full_unstemmed Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title_short Novel PKC-ζ to p47(phox) interaction is necessary for transformation from blebbishields
title_sort novel pkc-ζ to p47(phox) interaction is necessary for transformation from blebbishields
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819220/
https://www.ncbi.nlm.nih.gov/pubmed/27040869
http://dx.doi.org/10.1038/srep23965
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