Yang Yang, Wang Xiao-Le, Yue Ye-Xin, Chen Gang, Xia Hou-Fu
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China; TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
Cell Signal. 2025 Jan;125:111519. doi: 10.1016/j.cellsig.2024.111519. Epub 2024 Nov 20.
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.
肿瘤易感基因101（TSG101）于1996年首次被鉴定为一种肿瘤抑制因子。随后的研究逐渐揭示了它在包括细胞存活、囊泡运输、病毒感染等多个重要细胞过程中的关键作用。此外，TSG101在某些肿瘤发生过程中已被鉴定为一种癌蛋白。这些相互矛盾的发现表明TSG101可能表现出肿瘤异质性。目前，TSG101在口腔鳞状细胞癌（OSCC）中的表达模式和功能仍未被研究。在此，我们报道TSG101在OSCC患者中表达上调，且与较差的生存率和更高的淋巴结转移倾向相关。体内小鼠模型证实，TSG101的下调有效抑制了人OSCC细胞的肺转移。体外细胞实验不仅证明TSG101的敲低显著破坏了不同OSCC细胞系中与转移相关的表型，还揭示TSG101可能通过调节细胞周期蛋白A/B的转录来控制细胞周期，从而发挥这些作用。此外，我们用小鼠细胞系和小鼠原位OSCC模型进一步验证了这些发现。总的来说，本研究证实了TSG101在OSCC中的癌蛋白功能。我们为TSG101的异质性提供了新的见解，并突出了OSCC治疗的新潜在靶点。
