Abstract
We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of the matrix metalloproteinase 1 gene (MMP-1), MMP-13, and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Carcinoma, Renal Cell / genetics
-
Carcinoma, Renal Cell / mortality
-
Carcinoma, Renal Cell / pathology*
-
Cell Cycle Proteins / biosynthesis
-
Cell Cycle Proteins / genetics*
-
Cell Line, Tumor
-
Cell Movement / genetics
-
Cell Proliferation
-
Gene Expression Regulation, Neoplastic
-
Humans
-
Interferon-alpha / pharmacology
-
Kidney Neoplasms / genetics
-
Kidney Neoplasms / mortality
-
Kidney Neoplasms / pathology*
-
Matrix Metalloproteinase 1 / biosynthesis*
-
Matrix Metalloproteinase 13 / biosynthesis*
-
Neoplasm Invasiveness / genetics
-
RNA Interference
-
RNA, Messenger / biosynthesis
-
RNA, Small Interfering
Substances
-
Cell Cycle Proteins
-
Interferon-alpha
-
RNA, Messenger
-
RNA, Small Interfering
-
SLFN5 protein, human
-
MMP13 protein, human
-
Matrix Metalloproteinase 13
-
MMP1 protein, human
-
Matrix Metalloproteinase 1