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