SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with poor prognosis

Journal of Experimental & Clinical Cancer Research

Wei Chen¹  Guanghui Cheng²  Xiaoli Liu³  Yan Song⁴  Chunzheng Gao⁵  Xiuwen Wang⁵  Cheng Zhang⁵  Changliang Peng⁵  Jie Zhao⁵  Ji Li⁵  Dongjin Wu⁵  Hui Zhao⁶  Xiaoying Wang⁷ 

[1] Beijing Institute of Pharmacology and Toxicology;Central Research Laboratory, The Second Hospital of Shandong University, Shandong University;Department of Hematology, The Second Hospital of Shandong University, Shandong University;Department of Nephrology, The Second Hospital of Shandong University, Shandong University;Department of Orthopaedics, The Second Hospital of Shandong University, Shandong University;Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University;Department of Pathology, The Second Hospital of Shandong University, Shandong University;

关键词: SHCBP1;    EMT;    Synovial sarcoma;    Invasion;    Metastasis;    TGF-β1;   

DOI  :  10.1186/s13046-017-0616-z

来源: DOAJ

【 摘 要 】

Abstract Background Our previous studies reported that SHC SH2-domain binding protein 1 (SHCBP1) functions as an oncogene via promoting cell proliferations in synovial sarcoma (SS) cells. However, whether SHCBP1 has any effect on tumor metastasis remains unexplored. Methods The expression of SHCBP1 was analyzed in 76 SS tissues and two SS cell lines by immunohistochemistry and real-time RT-PCR. The relationship between SHCBP1 expression and the clinicopathological features of SS was investigated. The role of SHCBP1 in SS cell adhesion, migration, invasion and angiogenesis was explored by adhesion, Wound healing, Transwell, and Matrigel tube formation assays. Western blotting was conducted to detect the protein expressions of TGF-β1/Smad signaling pathway and EMT-related markers. The key molecules associated with migration, invasion and EMT were evaluated by immunohistochemistry in tumor specimens. Results In current study, we demonstrated that SHCBP1 overexpression significantly enhanced adhesion, migration, invasion and angiogenesis of SS cells. In contrast, SHCBP1 knockdown elicited the opposite effects on these phenotypes in vitro. SHCBP1 promoted tumor metastasis through inducing epithelial-mesenchymal transition (EMT) in SS cells. SHCBP1 knockdown could block the incidence of metastasis and EMT in SS cells. Furthermore, transforming growth factor-β1 (TGF-β1) induced SHCBP1 expression in a time-dependent pattern and SHCBP1 knockdown inhibited TGF-β1-induced EMT. The activation of the TGF-β1/Smad signaling pathway was involved in the oncogenic functions of SHCBP1 in SS. In addition, high expression of SHCBP1 in SS patients was associated with tumor progression and decreased survival as well as poor prognosis. Conclusions Taken together, our results indicate that SHCBP1 may promote the metastasis of SS by inducing EMT through targeting TGF-β1/Smad signaling pathway and can be a potential molecular target for SS therapy.

【 授权许可】

Unknown