Transforming growth factor-β1 signaling promotes epithelial-mesenchymal transition-like phenomena, cell motility, and cell invasion in synovial sarcoma cells

Abstract

The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithelial transition [MET]) have been shown to be associated with tumor cell invasion and metastasis in different carcinomas. The EMT and MET have recently been shown to play a key role in the pathogenic processes of sarcomas, which are completely different from those of carcinomas. However, the definitive roles of the EMT in the tumorigenesis of synovial sarcomas remain unknown. Here, we explored whether transforming growth factor (TGF)-β signaling, an important oncogenic event in synovial sarcoma, modulates tumor cell characteristics related to the EMT, such as cell adhesion, migration, invasion, and proliferation. Interestingly, we found that TGF-β1 induced tumor cell activation, resulting in a tendency to aggregate and biphasic-like features. TGF-β1 also caused downregulation of E-cadherin and subsequent upregulation of N-cadherin, Snail, and Slug, which are responsible for EMT-like phenomena and increased cell motility and invasion. To further investigate the roles of TGF-β1 in the EMT, we established a SW982 cell line with stable TGF-β1 inhibition viaSB431542.These cells exhibited significantly decreased motility, migration, and proliferation (P = 0.001). Taken together, our data demonstrated that alterations in the TGF-β1/Smad signaling pathway could regulate the expression of EMT-related factors and the EMT process, resulting in changes in tumor cell invasion, migration, and proliferation in synovial sarcoma cells. These results may provide a important insights into therapeutic interventions and contribute to the present understanding of tumor progression in patients.

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

“…Dramatic responses were observed with this drug in cervical cancers and pancreatic cancers, with an ongoing study including multiple expansion cohorts . In sarcomas, the role of TGF‐β is largely unexplored, though importance of stromal impact and crosstalk has been theorized preclinically in synovial sarcomas and osteosarcomas, where TGF‐β could play an important role in metastasis …”

Vitamin A Deficiency and the Lung

“…Historically, several stimuli from the local microenvironment, including growth factors and cytokines, inflammation, hypoxia, disruption of cell contact or contact with the surrounding ECM have been proposed as potential triggers of EMT. Although the molecular mechanisms underlying EMT in lung are still unclear, numerous studies have revealed that TGF-β signalling is a powerful inducer of EMT mostly through its canonical Smad-dependent pathway but also β-catenin signalling pathway seems to be involved [ 198 , 199 ]. This complex signalling network controls the expression of EMT markers.…”

Overexpression of carbonyl reductase 1 inhibits malignant behaviors and epithelial mesenchymal transition by suppressing TGF‑β signaling in uterine leiomyosarcoma cells

“…However, it is still controversial how TGF-β acts on sarcomas. Qi et al (35,45) reported that the TGF-β/Smad/Snail signaling pathway is closely associated with EMT, which promotes cell proliferation, migration, and invasion in synovial sarcomas. Dwivedi et al (46) showed that TGF-β promotes cell migration by phosphorylating Smad2 and Smad3 in uterine carcinosarcomas.…”

“…Regarding the mechanism of EMT, transforming growth factor (TGF)-β, which has roles in cell proliferation, differentiation, and tumorigenesis, has been reported to be closely associated with EMT in many epithelial and mesenchymal tumors (34,35). We previously analyzed pathways that are regulated by CBR1 in a uterine cervical cancer cell line overexpressing CBR1 (21).…”