Tspan7-KO Mouse

TSPAN7, a member of the tetraspanin family, has diverse functions. It acts as a positive regulator of actin nucleation and stabilization via the ARP2/3 complex, influencing processes like the transfer of HIV-1 from dendritic cells to T lymphocytes [1,8]. It also seems to be involved in the regulation of cell-cell interactions, cytoskeletal organization, and may impact various cellular functions related to development, immunity, and cancer [1,2,3,4,5,6,7,8,9,10]. Genetic models, such as knockout models, can be valuable for studying its role in more detail.

In Tspan7 knockout rats, ASD-like and ID-like behavioral phenotypes were observed, along with brain structure alterations and related pathological changes. The integrin β1/FAK/SRC signal pathway was interrupted, leading to down-regulation of key synaptic integrity-related proteins [7]. In glioma, TSPAN7 expression was decreased in high-grade gliomas, and low expression was associated with poor prognosis. Overexpression of TSPAN7 in glioma cell lines explored its anti-tumor role [2]. In bladder cancer, down-regulation of TSPAN7 was seen in tissues and cell lines, and overexpression in nude mice affected tumor growth via the PTEN/PI3K/AKT pathway [3]. In lung cancer, TSPAN7 promoted cell migration and proliferation via epithelial-to-mesenchymal transition [6]. In zebrafish, Tspan7 was required for migrasome formation, and its mutants showed impaired organ morphogenesis [5].

In conclusion, TSPAN7 is involved in a wide range of biological functions, including immune-related processes, organ morphogenesis, and synaptic function. Its role in diseases such as glioma, bladder cancer, lung cancer, and autism-spectrum disorder has been revealed through knockout models and other functional studies. These findings contribute to understanding the mechanisms of these diseases and may offer potential therapeutic targets.

References:

1. Ménager, Mickaël M. . TSPAN7, effector of actin nucleation required for dendritic cell-mediated transfer of HIV-1 to T cells. In Biochemical Society transactions, 45, 703-708. doi:10.1042/BST20160439. https://pubmed.ncbi.nlm.nih.gov/28620031/

2. Chen, Long, Liu, Hongwei, Li, Yanwen, Wanggou, Siyi, Li, Xuejun. 2023. Functional characterization of TSPAN7 as a novel indicator for immunotherapy in glioma. In Frontiers in immunology, 14, 1105489. doi:10.3389/fimmu.2023.1105489. https://pubmed.ncbi.nlm.nih.gov/36845098/

3. Yu, Xi, Li, Shenglan, Pang, Mingrui, Wang, Lei, Liu, Xiuheng. 2021. TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway. In Frontiers in oncology, 10, 613869. doi:10.3389/fonc.2020.613869. https://pubmed.ncbi.nlm.nih.gov/33489923/

4. Lu, Bingnan, Liu, Yifan, Yao, Yuntao, Pan, Xiuwu, Cui, Xingang. 2024. Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis. In Biology direct, 19, 72. doi:10.1186/s13062-024-00516-8. https://pubmed.ncbi.nlm.nih.gov/39175035/

5. 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/

6. Wang, Xianguo, Lin, Min, Zhao, Jinping, Xu, Ming, Zhou, Xuefeng. 2018. TSPAN7 promotes the migration and proliferation of lung cancer cells via epithelial-to-mesenchymal transition. In OncoTargets and therapy, 11, 8815-8822. doi:10.2147/OTT.S167902. https://pubmed.ncbi.nlm.nih.gov/30588007/

7. Pang, Shuo, Luo, Zhuohui, Dong, Wei, Zhang, Li, Zhang, Lianfeng. 2022. Integrin β1/FAK/SRC signal pathway is involved in autism spectrum disorder in Tspan7 knockout rats. In Life science alliance, 6, . doi:10.26508/lsa.202201616. https://pubmed.ncbi.nlm.nih.gov/36625203/

8. Perot, Brieuc P, García-Paredes, Victor, Luka, Marine, Ménager, Mickaël M. 2020. Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4+ T Lymphocytes. In Frontiers in cellular and infection microbiology, 10, 70. doi:10.3389/fcimb.2020.00070. https://pubmed.ncbi.nlm.nih.gov/32181159/

9. Huang, Runzhi, Sun, Hanlin, Lin, Ruoyi, Meng, Tong, Huang, Zongqiang. 2022. The role of tetraspanins pan-cancer. In iScience, 25, 104777. doi:10.1016/j.isci.2022.104777. https://pubmed.ncbi.nlm.nih.gov/35992081/

10. Bassani, Silvia, Passafaro, Maria. . TSPAN7: A new player in excitatory synapse maturation and function. In Bioarchitecture, 2, 95-97. doi:. https://pubmed.ncbi.nlm.nih.gov/22880149/