Abstract
BackgroundOur 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.MethodsThe 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.ResultsIn 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.ConclusionsTaken 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.
Highlights
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
Histological grade was used by the Federation Natinale des centres de Lutte Cotre le UICC International Union Against Cancer (Cancer) (FNCLCC) grading system, and disease stage according to the International Union Against Cancer (UICC) staging system
SHCBP1 gene expression in the two tested SS cell lines, human osteosarcoma cell line (Saos2), human hepatocarcinoma cell line (HepG2) and human breast cancer cell line (MCF-7) were significant upregulated (Fig. 1b), which is consistent with previous studies [19, 20]
Summary
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. Whether SHCBP1 has any effect on tumor metastasis remains unexplored. As a high-grade aggressive soft tissue tumor, synovial sarcoma (SS) accounts almost 10% in soft tissue sarcomas. Characterized by local recurrence and distant metastasis (found in more than 80% of SS patients), SS can occur almost anywhere in the body [2, 3]. The 5-year survival rate is estimated to be only around 27% to 55% with current available therapies including surgery, adjuvant chemotherapy and radiotherapy [4, 5]. No effective treatment is available currently to patients with metastasis, which often have a more poorer prognosis, and the 5-year overall survival rate usually lowers than 10% [6]. Elucidating the molecular mechanism involved in the metastasis of SS cell is desperately needed, which undoubtedly will greatly contribute to the development of novel therapeutic strategies for the treatment of SS
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