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Identification of SHCBP1 as a novel downstream target gene of SS18-SSX1 and its functional analysis in progression of synovial sarcoma.
- Source :
-
Oncotarget [Oncotarget] 2016 Oct 11; Vol. 7 (41), pp. 66822-66834. - Publication Year :
- 2016
-
Abstract
- The SS18-SSX1 fusion gene has been shown to play important roles in the development of synovial sarcoma (SS), but the underlying molecular mechanisms and its downstream target genes are still not clear. Here SHC SH2-domain binding protein 1 (SHCBP1) was identified and validated to be a novel downstream target gene of SS18-SSX1 by using microarray assay, quantitative real-time (qPCR) and western blot. Expression of SHCBP1 was firstly confirmed in SS cell line and SS tissues. The effects of SHCBP1 overexpression or knockdown on SS cell proliferation and tumorigenicity were then studied by cell proliferation, DNA replication, colony formation, flow cytometric assays, and its in vivo tumorigenesis was determined in the nude mice. Meanwhile, the related signaling pathways of SHCBP1 were also examined in SS cells. The results indicated that SHCBP1 was significantly increased in SS cells and SS tissues compared with adjacent noncancerous tissues. The expression of SHCBP1 was demonstrated to be positively correlated with the SS18-SSX1 level. Overexpression and ablation of SHCBP1 promoted and inhibited, respectively, the proliferation and tumorigenicity of SS cells in vitro. SHCBP1 knockdown also significantly inhibited SS cell growth in nude mice, and lowered the MAPK/ERK and PI3K/AKT/mTOR signaling pathways and cyclin D1 expression. Our findings disclose that SHCBP1 is a novel downstream target gene of SS18-SSX1, and demonstrate that the oncogene SS18-SSX1 promotes tumorigenesis by increasing the expression of SHCBP1, which normally acts as a tumor promoting factor.
- Subjects :
- Animals
Cell Cycle genetics
Cell Line, Tumor
Cell Proliferation genetics
Disease Progression
Gene Expression Profiling methods
Humans
Mice, Inbred BALB C
Mice, Nude
Oncogene Proteins, Fusion metabolism
RNA Interference
RNAi Therapeutics methods
Sarcoma, Synovial metabolism
Sarcoma, Synovial pathology
Shc Signaling Adaptor Proteins metabolism
Signal Transduction genetics
Xenograft Model Antitumor Assays methods
Gene Expression Regulation, Neoplastic
Oncogene Proteins, Fusion genetics
Sarcoma, Synovial genetics
Shc Signaling Adaptor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27572315
- Full Text :
- https://doi.org/10.18632/oncotarget.11651