Oncotarget. 2014 Dec 26. [Epub ahead of print]
Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression.
Baldwin RM1, Haghandish N1, Daneshmand M2, Amin S3, Paris G1, Falls TJ4, Bell JC5, Islam S3, Côté J1.
Abstract
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.
- PMID:
- 25605249
- [PubMed - as supplied by publisher]
Inga kommentarer:
Skicka en kommentar