SYT-SSX1 enhances the invasiveness and maintains stem-like cell properties in synovial sarcoma via induction of TGF-[beta]1/Smad signaling

• Published in: BMC cancer Vol. 22; no. 1
• Main Authors: Qi, Yan, Dong, Shuang-Shuang, He, Yong-Lai, Liu, Zi-Han, Huang, Ya-Lan, Wang, Ning, Zhang, Zhen, Li, Zhong, Shi, Mei Er Tu He Ta Mi, Feng, Xiao, Yao, Qing, Zou, Hong, Hu, Jian-Ming, Pang, Li-Juan, Li, Feng
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 12.02.2022
• Subjects: Analysis; Stem cells; Transforming growth factors; China
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09229-5

Background Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial-mesenchymal transition (EMT) via the TGF-[beta]1/Smad signaling pathway leads to SS metastasis. Methods We analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-[beta]1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-[beta]1 (a recombinant agent of the TGF-[beta]1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-[beta]1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells. Results It was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-[beta]1 and SB431542, we found that TGF-[beta]1 enhanced the proliferation of cells, induced EMT, and that TGF-[beta]1 enhanced the characteristics of tumor stem cells. Conclusions Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-[beta]1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment. Keywords: SYT-SSX1, Cancer stem cell, Synovial sarcoma, TGF-[beta]1/Smad, Signaling pathway, Epithelial-mesenchymal transition