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

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Patchett, AL ORCID: 0000-0002-8424-4680, Wilson, R ORCID: 0000-0003-0152-4394, Charlesworth, JC ORCID: 0000-0001-6201-3518, Corcoran, LM, Papenfuss, AT, Lyons, AB ORCID: 0000-0002-8508-5853, Woods, GM ORCID: 0000-0001-8421-7917 and Tovar, C ORCID: 0000-0001-9555-2489 2018 , 'Transcriptome and proteome profiling reveals stress-induced expression signatures of imiquimod-treated Tasmanian devil facial tumor disease (DFTD) cells' , OncoTarget, vol. 9, no. 22 , pp. 15895-15914 , doi: 10.18632/oncotarget.24634.

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Abstract

As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimodactivates tumor regression via stimulation of immune cell infiltration and cytotoxicresponses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells invitro, but a role for these effects in imiquimod-induced tumor regression remainsundefined. We previously demonstrated that cell lines derived from devil facial tumordisease (DFTD), a transmissible cancer threatening the survival of the Tasmaniandevil (Sarcophilus harrisii), are sensitive to imiquimod-induced apoptosis. In thisstudy, the pro-apoptotic effects of imiquimod in DFTD have been investigated usingRNA-sequencing and label-free quantitative proteomics. This analysis revealedthat changes to gene and protein expression in imiquimod treated DFTD cells areconsistent with the onset of oxidative and endoplasmic reticulum stress responses,and subsequent activation of the unfolded protein response, autophagy, cell cyclearrest and apoptosis. Imiquimod also regulates the expression of oncogenic pathways,providing a direct mechanism by which this drug may increase tumor susceptibilityto immune cytotoxicity in vivo. Our study has provided the first global analysis ofimiquimod-induced effects in any tumor cell line. These findings have highlightedthe potential of cell stress pathways as therapeutic targets in DFTD, and will allowfor improved mechanistic use of imiquimod as a therapy in both the Tasmanian deviland human cancers.

Item Type: Article
Authors/Creators:Patchett, AL and Wilson, R and Charlesworth, JC and Corcoran, LM and Papenfuss, AT and Lyons, AB and Woods, GM and Tovar, C
Keywords: imiquimod, Tasmanian devil, devil facial tumor disease, cancer, immunotherapy
Journal or Publication Title: OncoTarget
Publisher: Impact Journals LLC
ISSN: 1949-2553
DOI / ID Number: 10.18632/oncotarget.24634
Copyright Information:

Copyright: Patchett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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