Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression
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R. Mitchell Baldwin1,2, Nasim Haghandish1,2, Manijeh Daneshmand3,4, Shahrier Amin4,5, Geneviève Paris1,2, Theresa J. Falls3, John C. Bell3,6, Shahidul Islam4,5 and Jocelyn Côté1,2
1 Department of Cellular and Molecular Medicine, Ottawa, Ontario, Canada
2 Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3 Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4 Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada
5 Department of Pathology, Ottawa Hospital, Ottawa, Ontario, Canada
6 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Jocelyn Côté, email:
Keywords: Protein arginine methyltransferase, PRMT7, breast cancer, invasion, MMP9
Received: September 30, 2014 Accepted: December 18, 2014 Published: December 26, 2014
Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.
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