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The E3 Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity
Open accessAbstract
SUMMARY Understanding the mechanism underlying the regulation of the androgen receptor (AR), a central player in the development of castration-resistant prostate cancer (CRPC), holds promise for overcoming the challenge of treating CRPC. We demonstrate that the ubiquitin ligase Siah2 targets a select pool of NCOR1-bound, transcriptionally-inactive AR for ubiquitin-dependent degradation, thereby promoting expression of select AR target genes implicated in lipid metabolism, cell motility, and proliferation. Siah2 is required for prostate cancer cell growth under androgen-deprivation conditions in vitro and in vivo, and Siah2 inhibition promotes prostate cancer regression upon castration. Notably, Siah2 expression is markedly increased in human CRPCs. Collectively, we find that selective regulation of AR transcriptional activity by the ubiquitin ligase Siah2 is important for CRPC development.
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The mutational landscape of lethal castration-resistant prostate cancer
Grasso, C. S., Wu, Y.-M., Robinson, D. R., Cao, X., Dhanasekaran, S. M., Khan, A. P., Quist, M. J., Jing, X., Lonigro, R. J., Brenner, J. C., et al. (2012) · Nature · doi:10.1038/nature11125 · Cited by 2,517
TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
Bhowmick, N. A., Chytil, A., Plieth, D., Gorska, A. E., Dumont, N., Shappell, S., Washington, M. K., Neilson, E. G., & Moses, H. L. (2004) · Science · doi:10.1126/science.1090922 · Cited by 1,401
Self-citationFrasor, J., Danes, J. M., Funk, C. C., & Katzenellenbogen, B. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502782102 · Cited by 82
Cited by
Ubiquitin ligases in oncogenic transformation and cancer therapy
Senft, D., Qi, J., & Ronai, Z. A. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.105 · Cited by 489
Self-citationCopy number alteration burden predicts prostate cancer relapse
Hieronymus, H., Schultz, N., Gopalan, A., Carver, B. S., Chang, M. T., Xiao, Y., Heguy, A., Huberman, K., Bernstein, M., Assel, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411446111 · Cited by 364
Targeting ASCT2‐mediated glutamine uptake blocks prostate cancer growth and tumour development
Wang, Q., Hardie, R., Hoy, A. J., van Geldermalsen, M., Gao, D., Fazli, L., Sadowski, M. C., Balaban, S., Schreuder, M., Nagarajah, R., et al. (2015) · The Journal of Pathology · doi:10.1002/path.4518 · Cited by 338
Self-citationAn, J., Wang, C., Deng, Y., Yu, L., & Huang, H. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.013 · Cited by 260
USP22 regulates oncogenic signaling pathways to drive lethal cancer progression
Schrecengost, R. S., Dean, J. L., Goodwin, J. F., Schiewer, M. J., Urban, M. W., Stanek, T. J., Sussman, R. T., Hicks, J. L., Birbe, R. C., Draganova-Tacheva, R. A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1954 · Cited by 126
Metadata
- Authors
- Qi, J., Tripathi, M., Mishra, R., Sahgal, N., Fazil, L., Ettinger, S., Placzek, W. J., Claps, G., Chung, L. W. K., Bowtell, D., Gleave, M., Bhowmick, N., & Ronai, Z. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 23
- Issue
- 3
- Pages
- 332-346
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2012920679
- Cited by
- 158
- References
- 3
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: The E3 Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity. https://app.cochat.ai/papers/10.1016/j.ccr.2013.02.016
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- Qi, J., Tripathi, M., Mishra, R., Sahgal, N., Fazil, L., Ettinger, S., Placzek, W. J., Claps, G., Chung, L. W. K., Bowtell, D., Gleave, M., Bhowmick, N., & Ronai, Z. A. (2013). The E3 Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity. Cancer Cell. https://doi.org/10.1016/j.ccr.2013.02.016
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
