| Full text | |
| Author(s): Show less - |
Wu, Qin
;
Nie, David Y.
;
Ba-alawi, Wail
;
Ji, YiShuai
;
Zhang, ZiWen
;
Cruickshank, Jennifer
;
Haight, Jillian
;
Ciamponi, Felipe E.
;
Chen, Jocelyn
;
Duan, Shili
;
Shen, Yudao
;
Liu, Jing
;
Marhon, Sajid A.
;
Mehdipour, Parinaz
;
Szewczyk, Magdalena M.
;
Dogan-Artun, Nergiz
;
Chen, WenJun
;
Zhang, Lan Xin
;
Deblois, Genevieve
;
Prinos, Panagiotis
;
Massirer, Katlin B.
;
Barsyte-Lovejoy, Dalia
;
Jin, Jian
;
De Carvalho, Daniel D.
;
Haibe-Kains, Benjamin
;
Wang, XiaoJia
;
Cescon, David W.
;
Lupien, Mathieu
;
Arrowsmith, Cheryl H.
Total Authors: 29
|
| Document type: | Journal article |
| Source: | Nature Chemical Biology; v. N/A, p. 22-pg., 2022-05-16. |
| 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. (AU) | |
| FAPESP's process: | 15/25134-5 - Implementation of CLIP-seq computational analyzes for determination of target mRNAs and Caprin-1 protein binding sites |
| Grantee: | Felipe Eduardo Ciamponi |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 20/02006-0 - Molecular and structural characterization of RNA binding proteins acting as potential disease targets in cancer and neurology |
| Grantee: | Katlin Brauer Massirer |
| Support Opportunities: | Research Grants - Research Partnership for Technological Innovation - PITE |
| FAPESP's process: | 16/25521-1 - Computational analysis of transcriptomic alterations induced by stress granules in human cells |
| Grantee: | Felipe Eduardo Ciamponi |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/50897-0 - INCT 2014: Open-acess Medicinal Chemistry Centre (OpenMedChem) |
| Grantee: | Katlin Brauer Massirer |
| Support Opportunities: | Research Projects - Thematic Grants |