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Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells

As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro, but a role for these effects in imiquimod-induced t...

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Autores principales: Patchett, Amanda L., Wilson, Richard, Charlesworth, Jac C., Corcoran, Lynn M., Papenfuss, Anthony T., Lyons, Bruce A., Woods, Gregory M., Tovar, Cesar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882306/
https://www.ncbi.nlm.nih.gov/pubmed/29662615
http://dx.doi.org/10.18632/oncotarget.24634
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author Patchett, Amanda L.
Wilson, Richard
Charlesworth, Jac C.
Corcoran, Lynn M.
Papenfuss, Anthony T.
Lyons, Bruce A.
Woods, Gregory M.
Tovar, Cesar
author_facet Patchett, Amanda L.
Wilson, Richard
Charlesworth, Jac C.
Corcoran, Lynn M.
Papenfuss, Anthony T.
Lyons, Bruce A.
Woods, Gregory M.
Tovar, Cesar
author_sort Patchett, Amanda L.
collection PubMed
description As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro, but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil (Sarcophilus harrisii), are sensitive to imiquimod-induced apoptosis. In this study, the pro-apoptotic effects of imiquimod in DFTD have been investigated using RNA-sequencing and label-free quantitative proteomics. This analysis revealed that changes to gene and protein expression in imiquimod treated DFTD cells are consistent with the onset of oxidative and endoplasmic reticulum stress responses, and subsequent activation of the unfolded protein response, autophagy, cell cycle arrest and apoptosis. Imiquimod also regulates the expression of oncogenic pathways, providing a direct mechanism by which this drug may increase tumor susceptibility to immune cytotoxicity in vivo. Our study has provided the first global analysis of imiquimod-induced effects in any tumor cell line. These findings have highlighted the potential of cell stress pathways as therapeutic targets in DFTD, and will allow for improved mechanistic use of imiquimod as a therapy in both the Tasmanian devil and human cancers.
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spelling pubmed-58823062018-04-16 Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells Patchett, Amanda L. Wilson, Richard Charlesworth, Jac C. Corcoran, Lynn M. Papenfuss, Anthony T. Lyons, Bruce A. Woods, Gregory M. Tovar, Cesar Oncotarget Research Paper As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro, but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil (Sarcophilus harrisii), are sensitive to imiquimod-induced apoptosis. In this study, the pro-apoptotic effects of imiquimod in DFTD have been investigated using RNA-sequencing and label-free quantitative proteomics. This analysis revealed that changes to gene and protein expression in imiquimod treated DFTD cells are consistent with the onset of oxidative and endoplasmic reticulum stress responses, and subsequent activation of the unfolded protein response, autophagy, cell cycle arrest and apoptosis. Imiquimod also regulates the expression of oncogenic pathways, providing a direct mechanism by which this drug may increase tumor susceptibility to immune cytotoxicity in vivo. Our study has provided the first global analysis of imiquimod-induced effects in any tumor cell line. These findings have highlighted the potential of cell stress pathways as therapeutic targets in DFTD, and will allow for improved mechanistic use of imiquimod as a therapy in both the Tasmanian devil and human cancers. Impact Journals LLC 2018-03-23 /pmc/articles/PMC5882306/ /pubmed/29662615 http://dx.doi.org/10.18632/oncotarget.24634 Text en Copyright: © 2018 Patchett et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Patchett, Amanda L.
Wilson, Richard
Charlesworth, Jac C.
Corcoran, Lynn M.
Papenfuss, Anthony T.
Lyons, Bruce A.
Woods, Gregory M.
Tovar, Cesar
Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title_full Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title_fullStr Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title_full_unstemmed Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title_short Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells
title_sort transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated tasmanian devil facial tumor disease (dftd) cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882306/
https://www.ncbi.nlm.nih.gov/pubmed/29662615
http://dx.doi.org/10.18632/oncotarget.24634
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