Journal article
Potent Stimulation of the Androgen Receptor Instigates a Viral Mimicry Response in Prostate Cancer
M Alizadeh-Ghodsi, KL Owen, SL Townley, D Zanker, SPG Rollin, AR Hanson, R Shrestha, J Toubia, T Gargett, I Chernukhin, J Luu, KJ Cowley, A Clark, JS Carroll, KJ Simpson, JM Winter, MG Lawrence, LM Butler, GP Risbridger, B Thierry Show all
Cancer Research Communications | AMER ASSOC CANCER RESEARCH | Published : 2022
Abstract
Inhibiting the androgen receptor (AR), a ligand-activated transcription Increased ERV expression led to accumulation of double-stranded RNA factor, with androgen deprivation therapy is a standard-of-care treatment and a “viral mimicry” response characterized by activation of IFN signal-for metastatic prostate cancer. Paradoxically, activation of AR can also ing, upregulation of MHC class I molecules, and enhanced recognition of inhibit the growth of prostate cancer in some patients and experimen- murine prostate cancer cells by CD8+ T cells. Positive associations between tal systems, but the mechanisms underlying this phenomenon are poorly AR activity and ERVs/antiviral pathways were evident..
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Awarded by National Breast Cancer Foundation
Funding Acknowledgements
This work was supported by a Movember and National Breast Cancer Foundation Collaboration Initiative grant (MNBCF-17-012, to W.D. Tilley, G.P. Risbridger, J.S. Carroll, T.E. Hickey, and L.A. Selth) , the National Health and Medical Research Council of Australia (1145777, to W.D. Tilley, T.E. Hickey, andL.A. Selth; 1138242, to G.P. Risbridger, R.A. Taylor, W.D. Tilley, M.G. Lawrence, and L.A. Selth; and 1156570, to M.G. Lawrence and G.P. Risbridger) , The Hospital Research Foundation (2018-06-Strategic-R; T.E. Hickey, L.A. Selth, and W.D. Tilley) and the Cancer Council of South Australia (Beat Cancer Project Grant 1185012, to L.A. Selth) . The research programs of L.A. Selth, W.D. Tilley, and L.M. Butler are supported by the Movember Foundation and the Prostate Cancer Foundation of Australia through a Movember Revolutionary Team Award (MRTA3) . The research program of BSP was supported by Movember Prostate Cancer Research Alliance (PCRA) team funding (PRECEPT) . L.A. Selth and L.M. Butler are supported by Principal Cancer Research Fellowships (PRF2919 and PRF1117, respectively) awarded by Cancer Council's Beat Cancer project on behalf of its donors, the state Government through the Department of Health and the Australian Government through the Medical Research Future Fund. S.P.G. Rollin was the recipient of the Ralph Ernst PhD Scholarship, supported by Flinders Foundation. T.E. Hickey was supported by a fellowship from the National Breast Cancer Foundation (IIRS-19-009) . MAG was supported by an Australian Government Research Training Program Scholarship. R.A. Taylor and M.G. Lawrence were supported by Victorian Cancer Agency fellowships (MCRF15023 and MCRF18017) . G.P. Risbridger was supported by a National Health and Medical Research Council Fellowship (11027520) . The authors thank: Mark van der Hoek (South Australian Genomics Centre) for assistance with ChIP-seq and RNA-seq; and Zoya Kikhtyak, Geraldine Laven-Law, and Marie Pickering (University of Adelaide) for expert technical assistance. We are grateful to those men who donated specimens to the MU-RAL for provision of PDXs. The results published here are in part based on data generated by TCGA, established by the NCI and the National Human Genome Research Institute, and we are grateful to the specimen donors and relevant research groups associated with this project.