Open AccessDownregulation of SS18-SSX1 expression in synovial sarcoma by small interfering RNA enhances the focal adhesion pathway and inhibits anchorage-independent growth in vitro and tumor growth in vivo
Author(s) -
Satoshi Takenaka,
Norifumi Naka,
Nobuhito Araki,
Nobuyuki Hashimoto,
Takafumi Ueda,
Kiyoko Yoshioka,
Hiroyuki Yoshikawa,
Kazuyuki Itoh
Publication year - 2010
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000559
Subject(s) - small interfering rna , focal adhesion , downregulation and upregulation , microbiology and biotechnology , biology , gene silencing , synovial sarcoma , cell cycle , cancer research , signal transduction , transfection , cell , cell culture , pathology , sarcoma , medicine , biochemistry , genetics , gene
Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by a unique t(X;18) translocation resulting in expression of SS18-SSX fusion protein. In order to investigate the biological function of this fusion protein and to develop a novel therapeutic option, we examined downregulation of SS18-SSX1 expression by small interfering RNA targeting SS18-SSX1 in three human SS cell lines. Microarray analysis comparing SS18-SSX1-silenced cells with control cells in three SS cell lines showed that SS18-SSX1 mainly affected the focal adhesion pathway. In accord with the array data, silencing of SS18-SSX1 enhances adhesion to the extracellular matrix through the induction of expression of myosin light-chain kinase. Furthermore, the silencing of SS18-SSX1 inhibits anchorage-independent growth in vitro and systemic delivery of siRNA against SS18-SSX1 using a nanoparticle system inhibited tumor growth in a nude mouse xenograft model. Our results demonstrate that siRNA targeting of SS18-SSX1 has therapeutic potential for the treatment of SS.