title: Identification of SHCBP1 as a novel downstream target gene of SS18-SSX1 and its functional analysis in progression of synovial sarcoma.
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.
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Changliang
authors: C
authors: Peng
authors: Department of Orthopaedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Hui
authors: H
authors: Zhao
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Wei
authors: W
authors: Chen
authors: Nephrology Research Institute, Shandong University Second Hospital, Jinan, China.
authors: Yan
authors: Y
authors: Song
authors: Department of Pathology, Shandong University Second Hospital, Jinan, China.
authors: Xiaoying
authors: X
authors: Wang
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Ji
authors: J
authors: Li
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Yong
authors: Y
authors: Qiao
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Dongjin
authors: D
authors: Wu
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Shengzhong
authors: S
authors: Ma
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Xiuwen
authors: X
authors: Wang
authors: Department of Orthopaedics, Shandong University Second Hospital, Jinan, China.
authors: Chunzheng
authors: C
authors: Gao
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D015514:Oncogene Proteins, Fusion; C000599466:SHCBP1 protein, human; C587877:SS18-SSX1 fusion protein; D055765:Shc Signaling Adaptor Proteins
keywords: SHCBP1; SS18-SSX1; apoptosis; proliferation; synovial sarcoma