PRMT1 Regulates EGFR and Wnt Signaling Pathways and Is a Promising Target for Combinatorial Treatment of Breast Cancer

Cancers

David C. Silvestre¹  Samyuktha Suresh¹  Rayan Dakroub¹  Amélie Brisson¹  Mengliang Ye¹  Solène Huard¹  Thierry Dubois¹  Muriel Le Romancer²  Coralie Poulard²  David Gentien³  Cécile Reyes³  Hussein Fayyad-Kazan⁴  Elise Martel⁵  André Nicolas⁵  Didier Meseure⁵  Didier Decaudin⁶  Fariba Némati⁶  Sergio Roman-Roman⁷ 

[1] Breast Cancer Biology Group, Translational Research Department, Institut Curie-PSL Research University, 75005 Paris, France;Cancer Research Center of Lyon, CNRS UMR5286, Inserm U1052, University of Lyon, 69000 Lyon, France;Genomics Core Facility, Translational Research Department, Institut Curie-PSL Research University, 75005 Paris, France;Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut 1003, Lebanon;Platform of Experimental Pathology, Department of Diagnostic and Theranostic Medicine, Institut Curie-Hospital, 75005 Paris, France;Pre-Clinical Investigation Laboratory, Translational Research Department, Institut Curie-PSL Research University, 75005 Paris, France;Translational Research Department, Institut Curie-PSL Research University, 75005 Paris, France;

关键词: breast cancer;    EGFR;    PRMT1;    drug combinations;    Wnt signaling;   

DOI  :  10.3390/cancers14020306

来源: DOAJ

【 摘 要 】

Identifying new therapeutic strategies for triple-negative breast cancer (TNBC) patients is a priority as these patients are highly prone to relapse after chemotherapy. Here, we found that protein arginine methyltransferase 1 (PRMT1) is highly expressed in all breast cancer subtypes. PRMT1 depletion decreases cell survival by inducing DNA damage and apoptosis in various breast cancer cell lines. Transcriptomic analysis and chromatin immunoprecipitation revealed that PRMT1 regulates the epidermal growth factor receptor (EGFR) and the Wnt signaling pathways, reported to be activated in TNBC. PRMT1 enzymatic activity is also required to stimulate the canonical Wnt pathway. Type I PRMT inhibitors decrease breast cancer cell proliferation and show anti-tumor activity in a TNBC xenograft model. These inhibitors display synergistic interactions with some chemotherapies used to treat TNBC patients as well as erlotinib, an EGFR inhibitor. Therefore, targeting PRMT1 in combination with these chemotherapies may improve existing treatments for TNBC patients.

【 授权许可】

Unknown