Journal article
PRMT inhibition induces a viral mimicry response in triple-negative breast cancer
- Abstract:
- Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 7.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41589-022-01024-4
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Chemical Biology More from this journal
- Volume:
- 18
- Issue:
- 8
- Pages:
- 821–830
- Place of publication:
- United States
- Publication date:
- 2022-05-16
- Acceptance date:
- 2022-03-27
- DOI:
- EISSN:
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1552-4469
- ISSN:
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1552-4450
- Pmid:
-
35578032
- Language:
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English
- Keywords:
- Subjects:
- Pubs id:
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1260112
- Local pid:
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pubs:1260112
- Deposit date:
-
2023-06-14
Terms of use
- Copyright holder:
- Wu et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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