Tspan4, short for tetraspanin-4, is a key protein involved in the formation of migrasomes, a type of extracellular vesicle related to cell migration. It has been associated with the TGF-β1/Smad2/3 signaling pathway. Tspan4 is important in various biological processes such as organ morphogenesis, angiogenesis, and in the context of disease, it may be involved in the development of conditions like proliferative vitreoretinopathy (PVR), glioblastoma, and atherosclerosis [1,2,3,4,6]. Genetic models could potentially help further elucidate its functions.

In PVR, Tspan4-positive migrasomes derived from retinal pigmented epithelium (RPE) cells contribute to disease development. TGF-β1 in the PVR microenvironment increases Tspan4 expression, leading to migrasome production, which in turn enhances RPE cell migration and proliferation. Inhibiting Tspan4 in RPE cells reduces their ability to initiate experimental PVR [1]. In glioblastoma, Tspan4 promotes tumor progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Knockdown of Tspan4 in glioblastoma cells inhibits cell proliferation, invasion in vitro, and tumorigenicity in vivo [2]. In atherosclerosis, Tspan4 expression is upregulated in foam cells from patients, and high expression is associated with poor prognosis. Tspan4 expression is also highly associated with atherosclerosis regression-related macrophages, intraplaque hemorrhage, and ruptured plaques [3,4]. In embryonic angiogenesis, knockdown or knockout of Tspan4 in monocytes reduces migrasome formation, impairing capillary formation and monocyte recruitment [5].

In summary, Tspan4 plays a crucial role in the formation of migrasomes and is involved in several biological processes and disease conditions. Studies using gene knockout models in different cell types have revealed its functions in promoting cell migration, proliferation, and its association with poor prognosis in diseases like PVR, glioblastoma, and atherosclerosis. Understanding Tspan4 through these model-based researches provides potential therapeutic targets for these diseases.

References:

1. Wu, Liangjing, Yang, Shuai, Li, Hui, Wang, Zhaoyang, Wang, Fang. 2022. TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy. In Journal of nanobiotechnology, 20, 519. doi:10.1186/s12951-022-01732-y. https://pubmed.ncbi.nlm.nih.gov/36494806/

2. Dong, Yanbin, Tang, Xiaolong, Zhao, Wenhui, Chen, Juan, Liu, Yongshuo. 2024. TSPAN4 influences glioblastoma progression through regulating EGFR stability. In iScience, 27, 110417. doi:10.1016/j.isci.2024.110417. https://pubmed.ncbi.nlm.nih.gov/39108703/

3. Zheng, Yue, Lang, Yuheng, Qi, Bingcai, Gao, Wenqing, Li, Tong. 2023. TSPAN4 is a prognostic and immune target in Glioblastoma multiforme. In Frontiers in molecular biosciences, 9, 1030057. doi:10.3389/fmolb.2022.1030057. https://pubmed.ncbi.nlm.nih.gov/36685274/

4. Zheng, Yue, Lang, Yuheng, Qi, Bingcai, Li, Tong. . TSPAN4 and migrasomes in atherosclerosis regression correlated to myocardial infarction and pan-cancer progression. In Cell adhesion & migration, 17, 14-19. doi:10.1080/19336918.2022.2155337. https://pubmed.ncbi.nlm.nih.gov/36513632/

5. Zhang, Cuifang, Li, Tianqi, Yin, Shuyao, Wang, Jianbin, Yu, Li. 2022. Monocytes deposit migrasomes to promote embryonic angiogenesis. In Nature cell biology, 24, 1726-1738. doi:10.1038/s41556-022-01026-3. https://pubmed.ncbi.nlm.nih.gov/36443426/

6. Jiang, Dong, Jiang, Zheng, Lu, Di, Meng, Anming, Yu, Li. 2019. Migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulation. In Nature cell biology, 21, 966-977. doi:10.1038/s41556-019-0358-6. https://pubmed.ncbi.nlm.nih.gov/31371827/