Protein arginine methyltransferase 5: A novel therapeutic target for triple ‐negative breast cancers

Alternatives to current treatments are direly needed for patients with triple ‐negative breast cancers (TNBC). The present study endorses PRMT5 as a novel therapeutic target in TNBC. PRMT5 pharmacological inhibition decreases viability in a subset of TNBC cell lines, mitigates early‐stage tumor progression in vivo, and displays additive/synergistic effects in combination with EGFR inhibition. Importantly, this study shows distinctive PRMT5 subcellular localization in TNBC, underlining the importance of site‐specific PRMT5 activity in the context of breast cancers. AbstractTNBC is a highly heterogeneous and aggressive breast cancer subtype associated with high relapse rates, and for which no targeted therapy yet exists. Protein arginine methyltransferase 5 (PRMT5), an enzyme which catalyzes the methylation of arginines on histone and non ‐histone proteins, has recently emerged as a putative target for cancer therapy. Potent and specific PRMT5 inhibitors have been developed, but the therapeutic efficacy of PRMT5 targeting in TNBC has not yet been demonstrated. Here, we examine the expression of PRMT5 in a human breast cancer cohort obtained from the Institut Curie, and evaluate the therapeutic potential of pharmacological inhibition of PRMT5 in TNBC. We find that PRMT5 mRNA and protein are expressed at comparable levels in TNBC, luminal breast tumors, and healthy mammary tissues. However, immunohistochemistry analyses reveal that PRMT5 is differentially localized in TNB...

Source: Cancer Medicine - April 7, 2019 Category: Cancer & Oncology Authors: Mathilde Vinet, Samyuktha Suresh, Virginie Maire, Clarisse Monchecourt, Fariba N émati, Laetitia Lesage, Fabienne Pierre, Mengliang Ye, Auriane Lescure, Amélie Brisson, Didier Meseure, André Nicolas, Guillem Rigaill, Elisabetta Marangoni, Tags: ORIGINAL RESEARCH Source Type: research