TSG101 overexpression enhances metastasis in oral squamous cell carcinoma through cell cycle regulation.

Abstract

The tumor susceptibility gene 101 (TSG101) was firstly identified as a tumor-inhibiting factor in 1996. Subsequent studies gradually revealed its crucial role in several important cellular processes, including cell survival, vesicle transportation, viral infection, etc. Additionally, TSG101 has been identified as an oncoprotein in certain tumorigenic processes. These conflicting findings suggest that TSG101 might exhibit tumor heterogeneity. Currently, the expression pattern and function of TSG101 in oral squamous cell carcinoma (OSCC) are still untouched. Herein, we reported that TSG101 expression is upregulated and is associated with poorer survival and a higher propensity for lymph node metastasis in OSCC patients. In vivo mouse models confirmed that TSG101 down-regulation effectively inhibited the pulmonary metastases of human OSCC cells. In vitro cell experiments not only proved that TSG101 knockdown significantly disrupted metastasis-related phenotypes in different OSCC cell lines, but also revealed that TSG101 possibly controls the cell cycle through regulating the transcription of Cyclin A/B to play these roles. Additionally, we further validated these findings with a mouse cell line and murine orthotopic OSCC models. Collectively, the oncoprotein function of TSG101 in OSCC is evident from this study. We offer fresh insights into the heterogeneity of TSG101 and highlight new potential targets for OSCC management.